Question

Describe the process of coronavirus RNA replication including the proteins that are involved and their functions.

Answer 1

The CoVs has a single‐stranded positive‐sense RNA (+ssRNA) with 5′‐cap structure and 3′‐poly‐A tail.The coronavirus has a large RNA genome.

The major steps of the RNA replication are

• Ribosome frameshifting during translation
• Synthesis of genomic and subgenomic RNA species.

The CEACEM protein in the receptor cell plasma membrane binds with the S protein of the virus and  facilitate receptor mediated endocytosis.The genomic RNA will be then released into the cytoplasm of the host cell.

The RNA of the coronavirus gets translated by the host genomic mechanism.

step 1. The corona virus RNAs ORF is translated into polyproteins 1a and 1b.This are produced due to the frame shift during translation process.

step 2 :The polyproteins are proteolysed into a number of replicase/transcriptase proteins which combine with genomic RNA and causes the replication of the +RNA (sense RNA.)

step 3. The replication of the Sense RNA gives a -RNA (antisense RNA)strand

The antisense RNA can be replicated back to Sense RNA or Can be transcribed by discontinuous transcription into different subgenomic mRNA and the they can be translated to produce the various proteins.

step 4: The +RNA produced is then packed along with the viral proteins to produce the new progeny

Various structural and nonstructural proteins play a role in the Corona virus Replication.They are;

STRUCTURAL

• S proteins- Forms the spikes on the viral surface which are responsible for attachment to host receptors.
• M protein - shapes the virions, promotes membrane curvature, and binds to the nucleocapsid.
• E protein - Involved in virus assembly,release and viral pathogenesis.
• N protein - The domains can bind virus RNA genome .It is also an antagonist of interferon (IFN) and viral encoded repressor of RNA interference.

NON STRUCTURAL PROTEINS

nsp1 - Cellular mRNA degradation, inhibiting IFN signaling
nsp2-
nsp3 - polypeptides cleaving, blocking host innate immune response,Also promotes cytokine expression
nsp4 -formation of DMV
nsp5 -3CLpro, Mpro, polypeptides cleaving, inhibiting IFN signaling
nsp6 - autophagosome expansion restriction and DMV formation
nsp7 -Cofactor
nsp8 -Cofactor, primase
nsp9 -Dimerization and RNA binding
nsp10 - Scaffold protein for nsp14 and nsp16
nsp11 -
nsp12 -Primer dependent RdRp
nsp13 -RNA helicase
nsp14 -Exoribonuclease
nsp15 -Endoribonuclease and helps in evasion of dsRNA sensors
nsp16 -2′‐O‐MTase; avoiding MDA5 recognition, negatively regulating innate immunity