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Identification of recurrent mutations in exonuclease (nsp14); a potential drug target in SARS-CoV-2.
Jha, Deepak Kumar; Yashvardhini, Niti; Kumar, Amit.
  • Jha DK; Department of Zoology, P.C. Vigyan College, Chapra, Bihar, India.
  • Yashvardhini N; Department of Microbiology, Patna Women's College, Patna University, Patna, Bihar, India.
  • Kumar A; Department of Botany, Patna University, Patna, Bihar, India.
Indian J Pathol Microbiol ; 64(4): 771-775, 2021.
Article in English | MEDLINE | ID: covidwho-1485273
ABSTRACT
CONTEXT The rapid outbreak of SARS-CoV-2 has become a significant global health concern, highlighting the dire need for antiviral therapeutic agents. RNA-dependent RNA polymerase (RdRp) of coronavirus plays crucial roles in RNA synthesis, and hence remains the druggable target for the treatment of this disease. The most potent broad-spectrum inhibitors of viral RdRp are members of nucleoside analogs (NAs). However, SARS-CoV-2 proved to be a challenging one for the novel NA drug designing strategy because coronavirus possesses an exonuclease (ExoN) domain that is capable of excising NAs, thus showing resistance to existing antiviral drugs.

AIM:

The objective of our study was to compare the SARS-CoV-2 exonuclease (nsp14) protein sequence of Wuhan-type virus with those of Indian SARS-Cov-2 isolates and to study the effect of multiple mutations on the secondary structure alterations of proteins. SUBJECTS AND

METHODS:

Multiple-sequence alignment of exonuclease amino-acid sequences followed by phylogenetic analysis and prediction of its secondary structure of the protein was performed.

RESULTS:

Altogether, seven mutations were detected in the nsp14 of Indian SARS-CoV-2 isolates. Subsequently, prediction of their secondary structures revealed that mutations altered the structural stability of exonuclease proteins.

CONCLUSIONS:

Present findings, therefore, further suggest that evolvability of SARS-CoV-2 is primarily associated with the onset of multiple novel mutations that rapidly spread at several new locations of the viral genome and also provides important insight to develop specific control strategies to fight against COVID-19 infections.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Sequence Analysis, DNA / Exonucleases / SARS-CoV-2 / COVID-19 / COVID-19 Drug Treatment Type of study: Prognostic study / Randomized controlled trials Limits: Humans Country/Region as subject: Asia Language: English Journal: Indian J Pathol Microbiol Year: 2021 Document Type: Article Affiliation country: 0377-4929.328516

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Sequence Analysis, DNA / Exonucleases / SARS-CoV-2 / COVID-19 / COVID-19 Drug Treatment Type of study: Prognostic study / Randomized controlled trials Limits: Humans Country/Region as subject: Asia Language: English Journal: Indian J Pathol Microbiol Year: 2021 Document Type: Article Affiliation country: 0377-4929.328516