Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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.


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.


nsp12; RNA-dependent-RNA polymerase; SARS-CoV-2; inhibitor; vitamin B12


Medicine and Pharmacology, Pulmonary and Respiratory Medicine

Comments (0)

Comment 1
Received: 27 March 2020
Commenter: Pooja Darji
The commenter has declared there is no conflict of interests.
Comment: I think that if we denature the virus's spikes and envelope in the inactive form of virus with using some chemicals. For denaturing lipid layer and spikes we can use some buffer solutions or basic solutions or we can also use triton X 100. If once the envelope and spikes denatured then it's difficult for them to replicate it's genome or express their genomes.
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Comment 2
Received: 2 May 2020
Commenter: Gunjan Saboo
The commenter has declared there is no conflict of interests.
Comment: Hello

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

Gunjan Saboo
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