ScientificEuropean Contents

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VOL.

4/

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SSUE

3/

March

2021

I

SSN

2515-9534

(Pri

nt)

I

SSN

2515-9542

(Onl

i

ne)

Published by UK Education Consultancy services Ltd,(Company Number 10459935 Registered in England); Country of Publication: United Kingdom

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Space

Weat

her

,

Sol

ar

Wi

nd

Di

st

ur

bances

and

Radi

o

Bur

st

s

4

(2)

Sci

ent

i

f

i

c

Eur

opean

VOL.

4/

I

SSUE

3/

Mar

ch

2021

1)

Nasal

Spray

Vacci

ne

f

or

COVID-

19 5)

Ischgl

St

udy:

Devel

opment

of

Herd

Immuni

t

y

and

Vacci

ne

St

rat

egy

agai

nst

COVID-

19 7)

Mars

2020

Mi

ssi

on:

Perseverance

Rover

Successf

ul

l

y

Lands

on

t

he

Mars

Surf

ace

10)

mi

c

10)

mi

croRNAs:

New

Underst

andi

ng

of

Mech-ani

sm

of

Act

i

on

i

n

Vi

ral

Inf

ect

i

ons

and

i

t

s

Si

g-ni

f

i

cance

14)

Int

erf

eron-

β

f

or

Treat

ment

of

COVID-

19:

Subcut

aneous

Admi

ni

st

rat

i

on

more

Ef

f

ect

i

ve

16)

Space

Weat

her,

Sol

ar

Wi

nd

Di

st

urbances

and

Radi

o

Burst

s

20)

Cl

i

mat

e

Change:

Reduci

ng

Carbon

Emi

ssi

on

f

rom

Aeropl

anes

22)

Burden

of

Di

sease:

How

COVID-

19 has

Af

f

ect

ed

Li

f

e

Expect

ancy

24)

Genet

i

cs

of

COVID-

19:

Why

Some

Peopl

e

Devel

op

Severe

Sympt

oms

27)

Thapsi

gargi

n

(

TG)

:

A

Pot

ent

i

al

Ant

i

-

can-cer

and

Broad-

spect

rum

Ant

i

-

vi

ral

Agent

That

May

be

Ef

f

ect

i

ve

Agai

nst

SARS-

CoV-

2 Publ

i

sher’

s

st

at

ement

:

Sci

ent

i

f

i

c

European®

i

s

Bot

h

onl

i

ne

and

pri

nt

sci

ence

magazi

ne

publ

i

shed

by

UK

EPC

Lt

s,

(

Company

Number

10459935

Regi

st

ered

i

n

Engl

and)

;

ci

t

y:

Al

t

on,

Hampshi

re;

Count

ry

of

Publ

i

cat

i

on:

Uni

t

ed

Ki

ngdom.

,

ISSN

2515-

9534

(

Pri

nt

)

,

ISSN

2515-

9542

(

Onl

i

ne)

(3)

T

he emergence ofCOVID-19 asa pandemic triggered frantic research alloverthe world to combatthis pandemic by developing vaccinesin a race againsttime in orderto help countriesalloverthe world to return to normalcy assoon aspossible.A numberofpharmaceuticaland biotech companieshave been engaged in vaccine developmentand tilldate over300 vaccine projectshave been initiated and more than 40 projects are in clinicalevaluation while atleast5 ofthem have been approved asan emergency use authorization in diﬀerentcountries.Vaccineshave been made using diﬀerentapproachessuch aslive attenuate vaccine, mR-N

NA-based vaccine thatexpressesthe Spike protein ofthe virusaswellasAdenovirusbased vaccine that expressesseveralproteinsofthe virus.Allthese proteinsare expressed by the hostand in turn mountan

COVI

D-

19 Al

l

appr

oved

COVI

D-

19 vacci

nes

so

f

ar

e

admi

ni

st

er

ed

i

n

t

he

f

or

m

of

i

nj

ec-t

i

ons.

What

i

f

t

he

vacci

nes

coul

d

be

conveni

ent

l

y

del

i

ver

ed

as

spr

ay

i

n

t

he

nose?

I

f

you

do

not

l

i

ke

shot

s,

her

e

may

be

t

he

good

news!

I

nt

r

anasal

admi

ni

st

r

at

i

on

of

COVI

D-

19 vacci

ne

t

hr

ough

spr

ay

coul

d

soon

be

a

r

eal

i

t

y.

Cur

r

ent

l

y,

many

compani

es

ar

e

r

esear

chi

ng

on

expl

oi

t

i

ng

t

he

nasal

r

out

e

of

admi

ni

st

r

at

i

on

f

or

COVI

D-

19 vacci

nes,

some

of

whi

ch

ar

e

under

goi

ng

cl

i

ni

cal

t

r

i

al

s.

Thi

s

art

i

cl

e

di

scusses

t

he

pr

ogr

ess

made

i

n

t

hi

s

r

egar

d

wi

t

h

part

i

cul

ar

emphasi

s

on

t

he

use

of

at

t

enuat

ed

vi

r

uses

i

n

a

nasal

spr

ay

f

or

mul

at

i

on

agai

nst

COVI

D-

19.

Nasal

Spr

ay

Vacci

ne

f

or

COVI

D-

19

(4)

antibody response to the viralproteinsthereby providing protection. A

An alternative mode ofpreventing viralentry into the human body and delivering a vaccine candidate isto use the nasalroute.Severalresearchershave used nasalspray1 consisting ofsticky substancesthatcoatthe nasalmucuslining,thereby preventing the viralentry into the hostscells.Forexample,use ofnanoconj u-gate asnasalspray to deliverthe shRNA-plasmid to the targetsite 2.Intranasalroute foradministration of COVID-19 vaccine has been investigated by many researchers 3.There are several companies in the fore-frontin the use ofnasalspray technique foradministering ofvaccinesagainstCOVID-19.A few ofthese c

companiesuse the attenuated virus,while othersare using the adenovirusbased orinuenza-based vec-torsin the form ofnasalspray 4.

The companies that are exploiting the adenovirus, inuenza-based virus and Newcastle disease virus (NDV)5,6 based vectorsin a nasalspray formulation include Beijing AntaiBiolPharm Enterprise,China,two projectsfrom Acad MilSci,China,BharatBiotech-Washington Univ,India-US,AstraZeneca,Sweden-UK,Al -timmune,USA,Univ Hong Kong,Valavax-Abogn,China,Beijin VantalBiolPharm,China and LancasterUni -versity,UK.On the otherhand,companiesthatare utilizing attenuated virusin a nasalspray formulation i n-clude Codagenix,a New York based company in collaboration with The Serum InstofIndia,India,Indian

WWW.SCIENTIFICEUROPEAN.CO.UK

(5)

ImmunologicalsLtd,India,in collaboration with the Griﬃth University,Australia and MehmetAliAydunar Univ,Turkey.Ofparticularinterestare the companiesthatare using the attenuated whole virusin a nasal spray formulation asthe whole viruswillretain the capability ofmounting an immune response to the varied antigenspresentin the virusasopposed to only certain proteinsbeing targeted forantibody pr oduc-tion asisthe case with adenovirusbased,inuenza-based and Newcastle disease virus-based vaccines.This may potentially take care ofthe severalmutationsthe virusin undergoing aswell.In thisarticle,we will specically focuson the developmentand trialsforthe nasalspray vaccine thatuse the attenuated virus. T

The rstgroup thatusesattenuated virusin a nasalspray are researchersatCodagenix,USA whose vaccine isnamed COVI-VAC.The rstpatientin the randomised,double-blinded,placebo-controlled trialhasbeen dosed in January 2021.They have entered into collaboration with The Serum Institute ofIndia forthe manu-facture ofthisvaccine.The dose-escalation study hasbeen designed to evaluate the safety and tolerability ofthe vaccine in a totalof48 healthy volunteers.The study willalso assessthe ability ofthe vaccine to gener -ate an immune response which willbe assessed by measuring neutralising antibodies,mucosalimmunity in the airway and cellularimmunity.The vaccine can be stored easily in a refrigerator(2-8 C),can be adminis -tered easily withoutthe help ofskilled personneland ishopefully available asa single dose thatcan aﬀord protection.Thisalleviatesthe need forstorage and transportation atsub-zero temperaturesand can be readily given to a large numberofpeople ata time withoutthe need foradditionalequipmentand skilled personnel7.

Anothergroup atEureka Therapeuticshasdeveloped InvisiMask™ ,a Human Antibody NasalSpray which hasbeen successfully tested in preclinicalstudiesin mice withoutany signicantadverse eﬀects.The human monoclonalantibody bindsto the S1 Spike (S)protein ofSARS-CoV-2 virusand preventthem from binding to the angiotensin-converting enzyme 2 (ACE2)receptoron cellsin the upperrespiratory tract.This preventsthe virusfrom entering into human cellsand thereby preventsinfection.Anotherkey feature of thisvaccine isthatthe human monoclonalantibody used can bind and inhibitmore than 20 SARS-CoV-2 variants,including the highly infectiousD614G mutation 8,9.

T

These vaccinesbased on intra nasalspray route provide an excellentnon-invasive way ofadministering vac-cinesagainstSARS-CoV-2 virusand can be ofgreathelp in controlling the COVID-19 pandemic.There are severaladvantagesofusing the nasalspray route foradministering the vaccine.Nasalspray vaccine pr o-videsadditionallocalprotection atthe site ofadministration (mucosalimmunity based on secretory IgA and IgM and asa physicalbarrier)in addition to the systemic protection,in comparison to injected vaccine thatconfersonly systemic protection.People administered with intra muscularvaccinescan stillhave COVID-19 virusin theirnasalcavity and can transmititto others.

References:

1)Cavalcanti,I.D.L.,Cajubá de Britto Lira Nogueira,M.Pharmaceuticalnanotechnology:which productsare been designed againstCOVID-19?.JNanopartRes22,276 (2020).

https://doi.org/10.1007/s11051-020-05010-6

2)Prospective vaccination ofCOVID-19 using shRNA-plasmid-LDH nanoconjugate https://doi.org/10.1016/j.mehy.2020.110084

(6)

3)PolletJ.,Chen W.,and Strych U.,2021.Recombinantprotein vaccines,a proven approach againstcor ona-viruspandemics.Advanced Drug Delivery Reviews.Volume 170,March 2021,Pages71-82.

DOI:https://doi.org/10.1016/j.addr.2021.01.001

4)Forni,G.,Mantovani,A.,on behalfofthe COVID-19 Commission ofAccademia Nazionale deiLincei,Rome. etal.COVID-19 vaccines:where we stand and challengesahead.CellDeath Diﬀer28,626–639 (2021). Pub-lished:21 January 2021.

DOI:https://doi.org/10.1038/s41418-020-00720-9

5)University ofBirmingham 2020.News– Anti-COVID-19 nasalspray ‘ready foruse in humans’.Posted on 19 Nov 2020.Available online at

https://w w w.birm ingham .ac.uk/new s/latest/2020/11/an-ti-covid-19-nasal-spray-ready-for-use-in-humans.aspx

6)Park J,OladunniFS.,etal2021.Immunogenicity and Protective Eﬃcacy ofan IntranasalLive-attenuated Vaccine AgainstSARS-CoV-2 in PreclinicalAnimalModels.Posted January 11,2021.

doi:https://doi.org/10.1101/2021.01.08.425974

7) ClinicalTrial.gov 2020. Safety and Immunogenicity of COVI-VAC, a Live Attenuated Vaccine Against COVID-19.ClinicalTrials.gov Identier:NCT04619628.Available online at

https://clinicaltrials.gov/ct2/show/NCT04619628?term=COVI-VAC&cond=Covid19&draw=2&rank=1 8)Eureka Therapeutics,Inc.2020.PressRelease – Eureka TherapeuticsAnnouncesSuccessfulPreclinical Re-sultsofInvisimask™ Human Antibody NasalSpray AgainstSars-cov-2 Infection.Posted 14 December2020 Available from:

https://www.eurekatherapeutics.com/media/press-releases/121420/

9)Zhang H.,Yang Z.,etal2020.Intranasaladministration ofSARS-CoV-2 neutralizing human antibody pr e-ventsinfection in mice.PreprintbioRxiv .Posted 09 December2020.

DOI:https://doi.org/10.1101/2020.12.08.416677

(7)

T

he data from Ischglstudy demonstrated thatapprox.42.4% ofthe population were sero-positive after 9-10 monthsoftesting since rstpatientswere exposed to the corona virus1,2.However,thisrequiresthe use ofappropriate antibodiesand the righttargetto ensure thatindividualswith mild infectionsare not missed3.Thisdata from the Ischglstudy suggeststhatthe antibody response to COVID-19 isnotonly long lasting butcan be a predictorofherd immunity in a population.This,in turn,necessitatesthe need fora r ou-tine sero-surveillance in a population to estimate the numberofpeople who are antibody positive? Al -though thisstudy may notbe representative ofthe entire population,however,itcan stillhelp usin

COVI

D-

19 Rout

i

ne

ser

o-

survei

l

ance

of

t

he

popul

at

i

on

t

o

est

i

mat

e

pr

esence

of

a

ant

i

bodi

es

t

o

COVI

D-

19 i

s

r

equi

r

ed

t

o

under

st

and

t

he

devel

opment

of

her

d

i

mmuni

t

y

i

n

a

popul

at

i

on.

Dat

a

f

r

om

t

he

ser

o-

survei

l

ance

st

udy

of

popul

at

i

on

i

n

t

he

I

schgl

t

own

of

Aust

r

i

a

t

hr

ows

l

i

ght

on

t

hi

s

aspect

and

have

l

ed

r

esear

cher

s

t

o

devel

op

a

pr

edi

ct

i

on

model

whi

ch

coul

d

hel

p

pl

an

eﬀect

i

ve

vacci

ne

st

r

at

egy

and

non-

i

nvasi

ve

popul

at

i

on

i

nt

er

-vent

i

ons

agai

nst

t

he

i

nf

ect

i

on.

I

schgl

St

udy:

Devel

opment

of

Her

d

I

mmuni

t

y

and

Vacci

ne

St

r

at

egy

agai

nst

COVI

D-

19

(8)

In addition,thisstudy hasalso revealed the developmentofa non-invasive predictive modelbased on the self-assessmentofthree identied symptoms(cough,lossoftaste/smelland limb pain)thatcould accurately predictthe sero-positive individuals4 in a population thathasbeen infected by coronavirus. Exploitation ofsuch a non-invasive modelcan really be benecialto the entire world to ghtagainst the COVID-19 pandemic by predicting the sero-positivenessin the population.

C

Combining both these approachesofroutine sero-surveillance and predictive modelling using CHES software5 to determine sero-positiveness,countriesacrossthe world can eﬃciently plan sero-surveil -lance studiesthatcan help in controlling the pandemic by spending the tax-payersmoney more eﬀec-tively and bringing normalcy back assoon aspossible.

References:

1)Ischgl:Antibodiesonly decreased slightly.Published online on 18 February 2021.Available at https://tirol.orf.at/stories/3090797/Accessed on 19 February 2021.

2)Innsbruck MedicalUniversity 2021.Pressrelease – Ischglstudy:42.4 percentare antibody-positive. Available online at

https://www.i-med.ac.at/pr/presse/2020/40.htmlAccessed on 19 February 2021. 3)Are we underestimating seroprevalence ofSARS-CoV2.BMJ2020;370

doi:https://doi.org/10.1136/bmj.m3364 (Published 03 September2020) 4)

4)Lehmann,J.,Giesinger,etal.,2021.Estimating seroprevalence ofSARS-CoV-2 antibodiesusing three self-reported symptoms:Developmentofa prediction modelbased on data from Ischgl,Austria.Epi de-miology and Infection,1-13.Published online by Cambridge University Press:18 February 2021.DOI: https://doi.org/10.1017/S0950268821000418

5)HolznerB,GiesingerJM,Pinggera J,ZugalS,SchöpfF,OberguggenbergerAS,GamperEM,Zabernigg A,WeberB,Rumpold G.The Computer-based Health Evaluation Software (CHES):a software forel ec-tronic patient-reported outcome monitoring.BMC Med Inform DecisMak.2012 Nov 9;12:126.doi: https://doi.org/10.1186/1472-6947-12-126.

identifying,notonly the sero-positive individuals, but indirectly leads to predicting the estimated population thatwould require a boostervaccine dose ornot.Thisisofextreme importance atthis moment,given the factthatvaccine administr a-tion againstCOVID-19 isin fullswing in most coun-triesand the world iswaiting anxiously to return to the “normallife”thatexisted before COVID-19.This willenable the policy makersand administrators to develop guidelinesand ensure adequate health care resourcesare spenttowardsthe population where antibody developmentisminimal.

(9)

ASTRONOMY

&

SPACE

SCI

ENCE

Launched

on

30t

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Jul

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2020,

Per

sever

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over

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2021,

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om

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ggest

and

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best

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over

ever

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Mar

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once

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wat

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on

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Per

sever

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Rover

Successf

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Lands

on

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he

Mar

s

Surf

ace

(10)

Leave Earth before it’stoo late,CarlSagan had once warned in view ofremote possibility ofEarth being hit by an asteroid in future justthe way itwas65 million yearsago when dinosaurswere eliminated.Itmay be reasonable to think thatthe future ofhumanity liesin becoming space-faring species,in becoming a multi-planetspecies.And,here isan innitesimally smallstep in thatdirection towardsexploration of space fora betterunderstanding ofhabitable world 1.

T

The MarsroverPerseverance with itssophisticated robotic system specially designed to collectsamples hassuccessfully touched down on the Marssurface atJezero Crater.Thisplace wasonce wasa waterlake thatmay have nurtured primitive life formson Mars.The robotic system ofthe roverwillserve aseyesand armsofmankind forexploration on Marswhen itisnotpossible atthisjuncture to send astronauts.The Mars2020 Mission willsetup a seriesofmissionsin future forbringing the collected samplesto Earth for analysis2.

M

Marsonce had a thick atmosphere thatretained enough heatforwaterto remain in liquid state enabling running riversand lakeson itssurface.Thissuggeststhatprimitive microbiallife formsmay have existed on Mars.But,unlike Earth,Marsunfortunately doesnothave a magnetic eld to provide protection against powerfulsolarwind and ionising radiations.Asa result,itlostitsatmosphere to space in due course and the climate ofMarschanged to inhospitable frozen desertwith a very thin atmosphere oftoday 3.

(11)

The key briefofthisMars2020 mission isto search forthe signsofancientmicrobiallife thatmay have ex-isted on Marsbefore itsclimate changed to cold desert.Interestingly,in view ofthe detection ofmethane, itispostulated thatsome primitive life form may be presenton Marseven today.However,itrequires

con-rmation because methane may be released from non-living sourcesaswell.

Some ofcutting-edge instrumentsthatwillplay a key role in thisare SHERLOC and PIXL.Few otherswill help the roverto collectdata from a distance.Itispertinentto note thatthe roverhastouched down on the Martian surface atJezero Crater,which wasa waterlake in the pastmaking ita high potentialarea to supportmicrobiallife forms.The roverisalso collecting data aboutthe pastclimate and geology ofMars. Not

Notto missthe factthatthisMarsmission isnota round trip to Earth.The samplescollected by Persever -ance willpotentially be delivered to a planned landerin future which willbring the samplesto the Earth foranalysisto condirm the existence ofancientform oflife on Mars.

Importantly,Perseverance iscarrying severalinstrumentsand technologieswhose successfuluse in data collection and exploration on thismission,willpave the way forfuture missionsto the Moon and the Mars 4.

Sources:

1)Michio Kaku:3 mind-blowing predictionsaboutthe future.Available online athttps://youtu.be/t uVux-KTJeBI.Accessed on 18 February 2021.

2)Perseverance:Whatisso SpecialAboutthe RoverofNASA’sMission Mars2020.Scientic European. Available online at

https://www.scienticeuropean.co.uk/perseve ance-what-is-so-special-about-the-rover-of-nasas-mis -sion-mars-2020/Accessed on 18 February 2021.

3)NASA’sMAVEN RevealsMostofMars’Atmosphere WasLostto Space.Available online athttps:// ww-w.nasa.gov/press-release/nasas-maven-reveals-most-of-mars-atmosphere-was-lost-to-space. Accessed on 18 February 2021.

4)Thingsto Know Aboutthe Mars2020 Perseverance Mission.Available online athttps://www.jpl. na-sa.gov/news/press_kits/mars_2020/landing/.Accessed on 18 February 2021.

(12)

COVI

D-

19 Mi

cr

oRNAs

or

i

n

short

mi

RNAs

(

not

t

o

be

conf

used

wi

t

h

mRNA

or

messen-ger

RNA)

wer

e

di

scover

ed

i

n

1993

and

have

been

ext

ensi

vel

y

st

udi

ed

i

n

t

he

past

t

wo

decades

or

so

f

or

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(13)

MicroRNAsormiRNAshave gained popularity overthe pasttwo decadesfortheirrole in post-transcri p-tionalprocessessuch asdiﬀerentiation,metabolic homeostasis,proliferation and apoptosis(1-5).miRNAs are smallsingle-stranded RNA sequencesthatdo notencode forany proteins.They are derived from largerprecursors,which are double-stranded RNAs.The biogenesisofmiRNA startsin the nucleusofthe celland involvesgeneration ofprimary miRNA transcriptsby RNA polymerase IIfollowed by trimming of the primary transcriptto release the pre-miRNA hairpin by an enzyme complex.The primary miRNA is then

then exported to the cytoplasm where itisacted upon by DICER (a protein complex thatfurthercleaves the pre-miRNA),thereby producing the mature single-stranded miRNA.The mature miRNA integrates itselfaspartofthe RNA induced silencing complex (RISC)and inducespost-transcriptionalgene silencing by fastening RISC to the complementary regions,found within the 3’untranslated regions(UTRs),in the targetmRNAs.

The story began in 1993 with the discovery ofmiRNAsin C.elegansby Lee and hiscolleagues(6).Itwas observed thatthe LIN-14 protein wasdownregulated by anothertranscribed gene called lin-4 and this downregulation wasnecessary forthe larvaldevelopmentin C.elegansin progressing from stage L1 to L2.The transcribed lin-4 resulted in downregulating LIN-14 expression via complementary binding to the 3’UTR region oflin-4 mRNA,with little changesto mRNA levelsoflin-4.Thisphenomenon wasinitially thoughtto be exclusive and specic to C.elegans,untilabout2000,when they were discovered in other animal

animalspecies(7).Since then,there hasbeen a deluge ofresearch articlesdescribing the discovery and existence ofmiRNAsin both plantsand animals.Over25000 miRNAshave been discovered so farand for many,the exactrole they play in the biology ofthe organism stillremainselusive.

(14)

miRNAsexerttheireﬀectsby post-transcriptionally repressing the mRNAsby binding to complementary sitesin the 3’UTRsofthe mRNA they control.A strong complementarity earmarksthe mRNA fordegr ada-tion while a weak complementarity doesnotcause any changesin mRNA levelsbutcausesinhibition of translation.Although the majorrole ofmiRNA isin transcriptionalrepression,they also actasactivatorsin rare cases(8).miRNAsare play an indispensable role in the organism’sdevelopmentby regulating the genesand gene productsrightfrom the embryonic state to the developmentoforgan and organ systems (9-11).

(9-11).In addition to theirrole in maintaining cellularhomeostasis,miRNAshave also been implicated in variousdiseasessuch ascancer(miRNAsacting asboth activatorsand repressorofgenes),neurodegener -ative disordersand cardiovasculardiseases.Understanding and elucidating theirrole in variousdiseases can lead to new biomarkerdiscovery with concomitantnew therapeutic approachesfordisease pr even-tion.miRNAsalso play a criticalrole in the developmentand pathogenesisofinfectionscaused by mi -cro-organismssuch asbacteria and virusesby regulating the genesofthe immune system to mountan eﬀective response to the disease.In case ofviralinfections,Type Iinterferons(IFN alpha and IFN beta)are released asanti-viralcytokineswhich in turn modulatesthe immune system to mounta combative r e-sponse (12).The production ofinterferonsistightly regulated both atthe leveloftranscription and trans -lation and play a pivotalrole in determining the anti-viralresponse by the host.However,viruseshave evolved suﬃciently to deceive the hostcellsinto suppressing thisimmune response,providing advan-tage to the virusforitsreplication and thereby aggravating the disease symptoms(12,13).The tightc trolofinterplay between IFN production by the hostupon viralinfection and itssuppression by the infect -ing virusdeterminesthe extentand duration ofthe disease caused by the said virusin question.Although the transcriptionalcontrolofIFN production and related IFN stimulated genes(ISGs)iswellestablished (14),the mechanism oftranslationalcontrolhasstillremained elusive (15).

The recentstudy by researchersatthe McGillUniversity,Canada and the QueensUniversity,Belfastpr o-videsa mechanistic understanding ofthe translationalcontrolofIFN production thathighlightsthe role of4EHP protein in suppressing IFN-beta production and involvementofmiRNA,miR-34a.4EHP downr eg-ulatesIFN production by modulating the miR-34a-induced translationalsilencing ofIfnb1 mRNA.Inf ec-tion with RNA virusesand IFN beta induction increase the levelsofmiR-34a miRNA,triggering a negative feedback regulatory loop thatrepressesIFN beta expression via 4EHP (16).Thisstudy isofgreatsigni cance in the wake ofthe currentpandemic caused COVID-19 (an infection caused by an RNA virus)asit willhelp in furtherunderstanding ofthe disease and lead to novelwaysto dealwith the infection by mod-ulating the levelsofmiR-34a miRNA using designeractivators/inhibitorsand testing them in clinicaltrials foritseﬀectson IFN response.There have been reportsofclinicaltrialsutilising IFN beta therapy (17)and thisstudy willhelp unravelthe molecularmechanismsby highlighting the role ofmiRNA in intrinsically regulating the hosttranslationalmachinery formaintaining a homeostatic environment.

Future investigationsand research on such and otherknown and emerging miRNAscoupled with int e-gration ofthese ndingswith genomic,transcriptomic,and/orproteomic data,willnotonly enhance our mechanistic understanding ofthe cellularinteractionsand disease,butwould also lead to novelmiRNA based therapies by exploiting miRNA as actimirs (utilizing miRNAs as activators for replacement of miRNAsthathave been mutated ordeleted)and antagomirs(utilizing miRNAsasantagonistswhere there isabnormalupregulation ofthe said mRNA)forprevalentand emerging human and animaldiseases. References

Clairea T,Lamarthée B,Anglicheau D.MicroRNAs:smallmolecules,big eﬀects,CurrentOpinion in Organ Transplantation: February 2021 – Volume 26 – Issue 1 – p 10-16. DOI: https://doi.org/10.1097/ -MOT.0000000000000835

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2) Ambros V. The functions of animal microRNAs. Nature. 2004, 431 (7006): 350–5. DOI: https:// -doi.org/10.1038/nature02871

3)BartelDP.MicroRNAs:genomics,biogenesis,mechanism,and function.Cell.2004,116 (2):281–97.DOI: https://10.1016/S0092-8674(04)00045-5

4)Jansson M D and Lund A H MicroRNA and Cancer.MolecularOncology.2012,6 (6):590-610.DOI: https://doi.org/10.1016/j.molonc.2012.09.006

5)Bhaskaran M,Mohan M.MicroRNAs:history,biogenesis,and theirevolving role in animaldevelopment and disease.VetPathol.2014;51(4):759-774.DOI:https://doi.org/10.1177/0300985813502820

6)Rosalind C.Lee,Rhonda L.Feinbaum,VictorAmbros.The C.elegansheterochronic gene lin-4 encodes smallRNAswith antisense complementarity to lin-14,Cell,Volume 75,Issue 5,1993,Pages843-854,ISSN 0092-8674.DOI:https://doi.org/10.1016/0092-8674(93)90529-Y

7)PasquinelliA.,ReinhartB.,Slack F.etal.Conservation ofthe sequence and temporalexpression oflet-7 heterochronic regulatory RNA.Nature 408,86–89 (2000).DOI:https://doi.org/10.1038/35040556

8)

8)Vasudevan S,Tong Y and Steitz JA.Switching from Repression to Activation:MicroRNAsCan Up- Regu-late Translation.Science 21 Dec 2007:Vol.318,Issue 5858,pp.1931-1934.DOI:https://doi.org/10.1126/ -science.1149460

9)Bernstein E,Kim SY,CarmellMA,etal.Dicerisessentialformouse development.NatGenet.2003; 35:215–217.DOI:https://doi.org/10.1038/ng1253

10)Kloosterman WP,Plasterk RH.The diverse functionsofmicro-RNAsin animaldevelopmentand dis -ease.Dev Cell.2006;11:441–450.DOI:https://doi.org/10.1016/j.devcel.2006.09.009

11)WienholdsE,KoudijsMJ,van Eeden FJM,etal.The microRNA-producing enzyme Dicer1 isessentialfor zebrash development.NatGenet.2003;35:217–218.DOI:https://doi.org/10.1038/ng1251

12)HallerO,KochsG and WeberF.The interferon response circuit:Induction and suppression by pat ho-genic viruses.Virology.Volume 344,Issue 1,2006,Pages119-130,ISSN 0042-6822,

DOI:https://doi.org/10.1016/j.virol.2005.09.024

13)McNab F,Mayer-BarberK,SherA,Wack A,O’Garra A.Type Iinterferonsin infectiousdisease.NatRev Immunol.2015 Feb;15(2):87-103.DOI:https://doi.org/10.1038/nri3787

14)Apostolou,E.,and Thanos,D.(2008).Virusinfection inducesNF-kappa-B-dependentinterchromos om-al associations mediating monoallelic IFN-b gene expression. Cell 134, 85–96. DOI: https:// -doi.org/10.1016/j.cell.2008.05.052

15)Savan,R.(2014).Post-transcriptionalregulation ofinterferonsand theirsignaling pathways.J.Interfer -on Cytokine Res.34,318–329.DOI:https://doi.org/10.1089/jir.2013.0117

16) Zhang X, Chapat C et al. microRNA-mediated translational control of antiviral immunity by the cap-binding protein 4EHP. Molecular Cell 81, 1–14 2021. Published:February 12, 2021. DOI:https:// -doi.org/10.1016/j.molcel.2021.01.030

17)SCIEU 2021.Interferon-β forTreatmentofCOVID-19:SubcutaneousAdministration more Eﬀective.Scientic Eu-ropean. Posted on 12 February 2021. Available online on https://www.scienticeuropean.co.uk/interfer -on-β-for-treatment-of-covid-19-subcutaneous-administration-more-eﬀective/Accessed on 14 February 2021.

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NEWS

I

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T

he extraordinary situation presented by the COVID-19 pandemic haswarranted exploring diﬀerent possible avenuesforthe treatmentofsevere COVID-19 cases.Severalnew drugsare being tried and exist -ing drugsbeing repurposed.Corticosteroidshave already been found to be useful.Interferon therapy isal -ready in use forviralinfectionslike hepatitis.Can IFN be used againstSARS CoV-2 in COVID-19?

In preclinicaltrialsearlier,IFN had proved to be eﬀective againstSARS CoV and MERS viruses.In July 2020, administration ofInterferon-β through nebulisation (viz.pulmonary inhalation)route wasreported to show promising resultsin treating severe COVID-19 casesbased on data from phase 2 clinicaltrial1,2.

(17)

Now,the latestreportbased on data from phase 2 clinicaltrialconducted on 112 patientswith COVID-19 hospitalized atPitié-Salpêtrière in Paris,France suggeststhatadministration ofIFN-β through subcut ane-ousroute enhancesrecovery rate and decreasesmortality in COVID-19 cases3.

Interferons(IFN)are proteinssecreted by the hostcellsin response to viralinfectionsto signalthe other cellsforthe presence ofvirus.The exaggerated inammatory response in some ofthe COVID-19 patients isfound to be associated with impaired IFN-1 response and blockade IFN-β secretion.Itisused in China to treatviralpneumonia due to SARS CoV howeveritsuse isnotstandardised 4.

The phase 3 clinicaltrialforuse ofInterferons(IFN)in treatmentofsevere COVID-19 patientsiscurrently in progress.Approvalwilldepend on whetherthe nalresultsare within the acceptable range stipulated by the regulators.

Sources:

1)NHS 2020.Ne

1)NHS 2020.News-Inhaled drug preventsCOVID-19 patientsgetting worse in Southampton trial.Posted on 20 July 2020. Available online at https://www.uhs.nhs.uk/ClinicalResearchinSouthampton/ Re-search/News-and-updates/Articles/Inhaled-drug-prevents-COVID-19-patients-getting-worse-in-Southa mpton-trial.aspx Accessed on 12 February 2021.

2)Monk PD.,Marsden RJ.,TearVJ.,etal.,2020.Safety and eﬃcacy ofinhaled nebulised interferon beta-1a (SNG001)fortreatmentofSARS-CoV-2 infection:a randomised,double-blind,placebo-controlled,phase 2 trial.The LancetRespiratory Medicine,Available online 12 November2020.

DOI:https://doi.org/10.1016/S2213-2600(20)30511-7

3)Dorgham K.,Neumann AU.,etal2021.Considering personalized Interferon-β therapy forCOVID-19. An-timicrobialAgentsChemotherapy.Posted Online 8 February 2021.

DOI:https://doi.org/10.1128/AAC.00065-21

4)Mary A.,HénautL.,Macq PY.,etal2020.Rationale forCOVID-19 Treatmentby Nebulized Interfer -on-β-1b–Literature Review and PersonalPreliminary Experience.Frontiersin Pharmacology.,30 Novem-ber2020.DOI:https://doi.org/10.3389/fphar.2020.592543.

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Justthe way weatheron Earth isaﬀected by the disturbancesin the wind,space weather’isaﬀected by the disturbancesin the ‘solarwind’.Butthe similarity endshere.Unlike wind on Earth which ismade of aircomprising ofatmospheric gaseslike nitrogen,oxygen etc,the solarwind consistsofsuperheated plasma comprising ofelectrically charged particleslike electrons,protons,alpha particles(helium ions) and heavy ionsthatcontinuously emanate from the sun’satmosphere in alldirectionsincluding in the direction ofEarth.

Sun

Sun isthe ultimate source ofenergy to life on Earth hence respected in many culturesasgiveroflife.But there isotherside too.The solarwind,the continuousstream ofelectrically charged particles(viz. plasma)originating from the solaratmosphere posesthreatto the life on Earth.Thanksto Earth’s mag-netic eld thatdeectsmostofthe ionising solarwind away (from the Earth)and the Earth’sat mo-sphere thatabsorb mostofthe remaining radiation thusproviding protection from the ionising radi a-tion.Butthere ismore to it– in addition to threatto the biologicallife forms,solarwind also poses threatto electricity and technology driven modern society.The electronic and computersystems, powergrids,oiland gaspipelines,telecom,radio communication including mobile phone networks, GPS,space missionsand programmes,satellite communications,internetetc.– allthese can potentially be disrupted and broughtto standstillby disturbancesin solarwind1.Astronautsand the spacecrafts are particularly atrisk.There were severalinstancesofthisin the paste.g.,March 1989 ‘Quebec Bl ack-out‘in Canada caused due to massive solar are had badly damaged powergrid.Some satellitestoo had suﬀered damages.Therefore,the imperative to keep a watch on conditionsofthe solarwind in the vicinity ofthe Earth – how itscharacteristicslike speed and density,magnetic eld strength and ori en-tation,and energetic particle levels(i.e.,space weather)willhave an impacton life formsand modern human society.

Like ‘weatherprediction’,can ‘space weather’too be predicted? Whatdeterminesthe solarwind and its conditionsin the vicinity ofEarth? Can any seriouschangesin space weatherbe known in advance to take pre-emptive actionsto minimise damaging impacton Earth? And,why atalldoesthe solarwind form?

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Sun isa ballofhotelectrically charged gasand therefore,itdoesnothave a denite surface.The phot o-sphere layeristreated assurface ofthe sun because thisiswhatwe can observe with light.Layersbelow the photosphere inwardstowardsthe core are opaque to us.Solaratmosphere ismade oflayersabove the photosphere surface ofthe sun.Itisthe transparentgaseoushalo surrounding the Sun.Betterseen from the Earth during the totalsolareclipse,solaratmosphere hasfourlayers:chromosphere,solartr an-sition region,corona and heliosphere.

Solarwind isformed in corona,the second layer(from outside)ofthe solaratmosphere.Corona isa layerofvery hotplasma.While the temperature ofthe surface ofthe Sun isabout6000K,the average temperature ofcorona isabout1-2 million K.Called ‘CoronalHeating Paradox’,the mechanism and the processesofheating ofcorona and acceleration ofthe solarwind to very high speed and expansion into interplanetary space isnotwellunderstood yet,2 though in a recentpaper,researchershave soughtto solve thisby way ofaxion (the hypotheticaldark matterelementary particle)origin photons 3.

O

Occasionally,huge amountofhotplasma isejected from corona into the outermostlayerofsolarat mo-sphere (heliosphere).Called CoronalMassEjections(CMEs),the massejectionsofplasma from corona are found to generate large disturbancesin solarwind temperature,velocity,density and interpl ane-tary magnetic eld.These create strong magnetic stormsin the geomagnetic eld ofthe Earth 4.Er up-tion ofplasma from corona involvesacceleration ofelectronsand acceleration ofcharged particles gen-eratesradio waves.Asa result,CoronalMassEjections(CMEs)isalso associated with burstsofradio sig nalsfrom the Sun 5.Therefore,space weatherstudieswould involve study oftiming and intensity of massejectionsofplasma from the corona in conjunction with the associated solarburstswhich isa Type IV radio burstlasting forlong-duration (greaterthan 10 min.).

The occurrence ofradio burstsin the earliersolarcycles(the periodic cycle ofSun’smagnetic eld every 11 years)in relation to CoronalMassEjections(CMEs)hasbeen studied in the past.

One recentlong-term statisticalstudy by Anshu Kumarietal.ofUniversity ofHelsinkion radio bursts observed in the solarcycle 24,shedsfurtherlighton association oflong-duration,widerfrequency radio bursts(called type IV bursts)with CMEs.The team found thatabout81% ofthe type IV burstswere followed by coronalmassejections(CMEs).About19% oftype IV burstswere notaccompanied by CMEs.In addition,only 2.2% ofthe CMEsare accompanied by type IV radio bursts6.

Understanding

Understanding the timing oftype IV long duration burstsand the CMEsin an incrementalmannerwill help in the design and timing ofthe ongoing and future space programsaccordingly,so asto lessen the impactofthese on such missionsand ultimately on the life formsand the civilization on Earth.

References:

1)White SM.,nd.SolarRadio Burstsand Space Weather.University ofMaryland.Available online at https://www.nrao.edu/astrores/gbsrbs/Pubs/AJP_07.pdfAccessed on 29 Jamaury 2021.

2)

2)Aschwanden MJetal2007.The CoronalHeating Paradox.The AstrophysicalJournal,Volume 659, Number2.DOI:https://doi.org/10.1086/513070

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3)Rusov VD,Sharph IV,etal2021.Coronalheating problem solution by meansofaxion origin pho-tons.Physicsofthe Dark Universe Volume 31,J anu-ary 2021, 100746. DOI: https:// -doi.org/10.1016/j.dark.2020.100746

4)Verma PL.,etal2014.CoronalMassEjectionsand Disturbancesin SolarWind Plasma Parametersin Relation with Geomagnetic Storms. Journal of Physics:Conference Series511 (2014)012060.DOI: https://doi.org/10.1088/1742-6596/511/1/012060 5)

5) Gopalswamy N., 2011. Coronal Mass Ejections and Solar Radio Emissions. CDAW Data Center NASA. Available online at https://cdaw.gsfc. na-sa.gov/publications/gopal/gopal2011Pl ane-RadioEmi_book.pdfAccessed on 29 January 2021. 6)KumariA.,Morosan DE.,and Kilpua EKJ.,2021. On the Occurrence ofType IV SolarRadio Burstsin SolarCycle 24 and TheirAssociation with Coronal MassEjections.Published 11 January 2021.The As -trophysicalJournal,Volume 906,Number2.DOI: https://doi.org/10.3847/1538-4357/abc878

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NEWS

I

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BRI

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Car

bon

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C

ommercialaircraftsuse lotoffuelsto generate suﬃcientpowerto sustain ight.The burning ofavi -ation fuelscontributesin greenhouse gasesin the atmosphere which in turn isresponsible forglobal warming and climate change.Currently,carbon emission from aeroplanesconstitutesabout2.4% ofall man-made sourcesofCO2.This gure islikely to grow with growth in aviation sector.Hence the imper a-tive to explore novelwaysto reduce carbon emission from airlinersand to enhance eﬃciency.Several wayshave been thoughtofto reduce the carbon emission from aeroplanes.One such isto take the ad-vantage ofdirection ofthe wind especially in the long-haul ights.

The idea ofusing wind direction in aviation to reduce fueluse isnotnew butithad limitations.Advances in space and atmospheric scienceshasnow enabled fullsatellite coverage and globalatmospheric dat a-set.The research team ofUniversity ofReading hasfound thatthe transatlantic ightsbetween London and New York could save up to 16% offuelthrough betteruse ofwind direction.The team analysed about 35000 transatlantic ightsbetween 1 December2019 and 29 February 2020 and used optimalcontrol theory to nd the minimum time routes.The ndingsindicated to a gap ofhundredsofkilometres be-tween typicalactual ightpathsand fueloptimised paths.Thisupdate could help reduce carbon emis -sion in shortterm withoutinvolving any new capitaloutlay fortechnologicaladvances.

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Source:

WellsCA,WilliamsPD.,etal2021.Reducing transatlantic ightemissionsby fuel-optimised routing. EnvironmentalResearch Letters,Volume 16,Number2.Published 26 January 2021.

DOI:https://doi.org/10.1088/1748-9326/abce82

Pages91-103,DOI;https://doi.org/10.1016/j.j con-rel.2017.07.026

Lam JH.,Khan AK.,etal2021.Nextgeneration vac-cine platform:polymersomesasstable nanocarri -ers for a highly immunogenic and durable SARS-CoV-2 spike protein subunit vaccine. Pr e-print. bioRxiv 2021.01.24.427729; Posted January 25, 2021. DOI: https:// -doi.org/10.1101/2021.01.24.427729