Article
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Vitamin B12 May Inhibit RNA-Dependent-RNA Polymerase Activity of nsp12 from the SARS-CoV-2 Virus
Version 1
: Received: 22 March 2020 / Approved: 23 March 2020 / Online: 23 March 2020 (07:46:54 CET)
A peer-reviewed article of this Preprint also exists.
Abstract
SARS-CoV-2 is the causative agent for the ongoing COVID19 pandemic, and this virus belongs to the Coronaviridae family. Like other members of this family, the virus possesses a positive-sense single-stranded RNA genome. The genome encodes for the nsp12 protein, which houses the RNA-dependent-RNA polymerase (RdRP) activity responsible for the replication of the viral genome. A homology model of nsp12 was prepared using the structure of the SARS nsp12 (6NUR) as a model. The model was used to carry out in silico screening to identify molecules among natural products, or FDA approved drugs that can potentially inhibit the activity of nsp12. This exercise showed that vitamin B12 (methylcobalamin) may bind to the active site of the nsp12 protein. A model of the nsp12 in complex with substrate RNA and incoming NTP showed that Vitamin B12 binding site overlaps with that of the incoming nucleotide. A comparison of the calculated energies of binding for RNA plus NTP and methylcobalamin suggested that the vitamin may bind to the active site of nsp12 with significant affinity. It is, therefore, possible that methylcobalamin binding may prevent association with RNA and NTP and thus inhibit the RdRP activity of nsp12. Overall, our computational studies suggest that methylcobalamin form of vitamin B12 may serve as an effective inhibitor of the nsp12 protein.
Keywords
nsp12; RNA-dependent-RNA polymerase; SARS-CoV-2; inhibitor; vitamin B12
Subject
Medicine and Pharmacology, Pulmonary and Respiratory Medicine
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Commenter: Pooja Darji
The commenter has declared there is no conflict of interests.
Commenter: Gunjan Saboo
The commenter has declared there is no conflict of interests.
Your study is very encouraging.
Has any trial of any kind done further based on
your study for Vitamin B12.
Please reply to my email gunjansaboo@yahoo.com
Regards
Gunjan Saboo