Published 19:11 IST, August 12th 2020

Scientists come up with atomic-level resolution view of coronavirus' replication system

RNA virus can be seen with irregular spikes with typically larger RNA genome and “never known previously” replication strategy in Atomic-Level Resolution.

Science News
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In a new study published in Cell, researchers at Rockefeller have got a step closer to the crucial mystery of the fast-spreading SARS-CoV-2's contagion after they traced its atomic-level resolution view of its replication system. In the first-ever image of the coronavirus’ genetic material, the RNA virus can be seen with irregular spikes that protrude from the surface with typically larger RNA genome and “never known previously” replication strategy.

As per the research, the scientists have discovered a new structural template of the COVID-19 causing virus which will lead a pathway for developing chemical compounds that can enter and destroy its molecular structure. As per the research, the SARS-CoV-2 genome (29.8 kb) codes for 10 genes to produce 26 proteins. These genes are arranged in the order 5′-replicase-S-E-M-N-3′, with genes for accessory proteins interspersed among structural ones (S, E, M, N). However, scientists found that about two-thirds of the entire RNA is occupied by the polymerase gene, which has two overlapping open reading frames (ORFs). The entry of the virus to host cells is mediated by S protein, which recognizes angiotensin-converting enzyme ACE2 in the host and binds with it.

This tight cluster of RdRp and associated proteins is likely what the enzyme looks like outside the lab and in its native environment, inside an infected cell, a postdoctoral associate in Seth Darst's lab and one of the study's first authors, James Chen said in the journal.

We now have an additional structural template that can be really helpful for drug developers trying to find new compounds that could get into this molecular machine and make it stop, a research associate professor at Rockefeller, Elizabeth Campbell said in the study.

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[The virus is enveloped and spherical (~120 nm in diameter), with petal-shaped surface spikes (~20 nm long). Key structural proteins, spike (S), envelope (E), and membrane (M), are anchored on the viral envelope. Credit: Cell Journal]

Enzyme ‘RNA-dependent RNA polymerase’

In the new study, researchers focused on obtaining a clearer picture of mutations and the global evolution of different strains. It was found that the coronavirus copies its genetic material with the help of an enzyme called ‘RNA-dependent RNA polymerase’, or RdRp. The virus’ replication machinery is powered by this enzyme, and this is what the antiviral drugs like remdesivir attack, the research revealed. Scientists were able to figure out details of the fundamental copy operations of the coronavirus, and RdRp molecule. In what can be called the barrier to developing a compound to stop this replication is the fact that the RdRp molecule does not function alone. Scientists, in the first-ever, detected the silent fuel enzyme called the Helicase, which, in fact, is a target for COVID-19 drug discovery.