Emerging genetic diversity of SARS-CoV-2 RNA dependent RNA polymerase (RdRp) alters its B-cell epitopes

Kumar, Sushant; Kumari, Khushboo; Azad, Gajendra Kumar

doi:10.1016/j.biologicals.2021.11.002

Cited by 9 publications

(3 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other amino acid substitutions such as V405F (BA.2.75), Y273H (BQ.1.1 and BQ.1.5), A529V (XAY.1 and XBC), and ins823D (XBC) were identified in Nsp 12. A529V, V405F, X823D, and Y273H substitutions were previously reported, where their frequency was approximately 1%, and did not affect the binding of remdesivir (Pitts et al, 2022;Vangeel et al, 2022;Kumar et al, 2022;Imai et al, 2023). Moreover, they did not include the most important residues for RdRp binding (Nguyen et al, 2020).…”

Section: Textmentioning

confidence: 87%

Evaluation of antiviral drugs against newly emerged SARS-CoV-2 Omicron subvariants

Cho¹,

Shin²,

Yang³

et al. 2023

Preprint

View full text Add to dashboard Cite

The ongoing emergence of SARS-CoV-2 Omicron subvariants and their rapid worldwide spread pose a threat to public health. From November 2022 to February 2023, newly emerged Omicron subvariants, including BQ.1.1, BF.7, BA.5.2, XBB.1, XBB.1.5, and BN.1.9, became prevalent global strains (>5% global prevalence). These Omicron subvariants are resistant to several therapeutic antibodies. Thus, the antiviral activities of current drugs such as remdesivir, molnupiravir, and nirmatrelvir, which target highly conserved regions of SARS-CoV-2, against newly emerged Omicron subvariants need to be evaluated. We assessed the antiviral efficacy of the drugs using half maximal inhibitory concentration (IC50) against human isolated 23 Omicron subvariants and four former SARS-CoV-2 variants of concern (VOC) and compared them with the antiviral efficacy of these drugs against the SARS-CoV-2 reference strain (hCoV/Korea/KCDC03/2020). Maximal IC50 fold changes of remdesivir, molnupiravir, and nirmatrelvir were 1.9- (BA.2.75.2), 1.2- (B.1.627.2), and 1.4-fold (BA.2.3), respectively, compared to median IC50 values of the reference strain. Moreover, median IC50-fold changes of remdesivir, molnupiravir, and nirmatrelvir against the Omicron variants were 0.96, 0.4, and 0.62, similar to 1.02, 0.88, and 0.67, respectively, of median IC50-fold changes for previous VOC. Although K90R and P132H in Nsp 5, and P323L, A529V, G671S, V405F, and ins823D in Nsp 12 mutations were identified, these amino acid substitutions did not affect drug antiviral activity. Altogether, these results indicated that the current antivirals retain antiviral efficacy against newly emerged Omicron subvariants, and provide comprehensive information on the antiviral efficacy of these drugs. Keywords: SARS-CoV-2, Omicron subvariant, remdesivir, molnupiravir, nirmatrelvir, antiviral activity

show abstract

Section: Textmentioning

confidence: 87%

Evaluation of antiviral drugs against newly emerged SARS-CoV-2 Omicron subvariants

Cho¹,

Shin²,

Yang³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…We used freely accessible CoVal database ( https://coval.ccpem.ac.uk/ ) to retrieve mutations of SARS-CoV-2 reported from India as described earlier. 29 CoVal database has been recently developed and serve as a repository of amino acid replacement mutations identified in the SARS-CoV-2 genome sequences reported from different countries worldwide. Furthermore, we analysed all SARS-CoV-2 isolates sequences (50217) reported from India till September 2021 and our data revealed that a total 182 mutations have occurred in this protein.…”

Section: Methodsmentioning

confidence: 99%

An immunoinformatics approach to study the epitopes of SARS-CoV-2 helicase, Nsp13

Kumar

Kumari

Azad

2023

Vacunas

Self Cite

View full text Add to dashboard Cite

“…The structural modeling was performed using ‘normal mode’ in the Phyre2 programme. The visualisation of the predicted protein structure obtained from Phyre2 was conducted using the ChimeraX tool [ 31 ] as described earlier [ 32 – 34 ].…”

Section: Methodsmentioning

confidence: 99%

A computational study on mitogenome-encoded proteins of Pavo cristatus and Pavo muticus identifies key genetic variations with functional implications

Yasmin

Kumar

Azad

2023

Journal of Genetic Engineering and Biotechnology

Self Cite

View full text Add to dashboard Cite

Background The Pavo cristatus population, native to the Indian subcontinent, is thriving well in India. However, the Pavo muticus population, native to the tropical forests of Southeast Asia, has reduced drastically and has been categorised as an endangered group. To understand the probable genetic factors associated with the decline of P. muticus, we compared the mitogenome-encoded proteins (13 proteins) between these two species. Results Our data revealed that the most frequent variant between these two species was mtND1, which had an alteration in 9.57% residues, followed by mtND5 and mtATP6. We extended our study on the rest of the proteins and observed that cytochrome c oxidase subunits 1, 2, and 3 do not have any change. The 3-dimensional structure of all 13 proteins was modeled using the Phyre2 programme. Our data show that most of the proteins are alpha helical, and the variations observed in P. muticus reside on the surface of the respective proteins. The effect of variation on protein function was also predicted, and our results show that amino acid substitution in mtND1 at 14 sites could be deleterious. Similarly, destabilising changes were observed in mtND1, 2, 3, 4, 5, and 6 and mtATP6–8 due to amino acid substitution in P. muticus. Furthermore, protein disorder scores were considerably altered in mtND1, 2, and 5 of P. muticus. Conclusions The results presented here strongly suggest that variations in mitogenome-encoded proteins of P. cristatus and P. muticus may alter their structure and functions. Subsequently, these variations could alter energy production and may correlate with the decline in the population of P. muticus.

show abstract

Emerging genetic diversity of SARS-CoV-2 RNA dependent RNA polymerase (RdRp) alters its B-cell epitopes

Cited by 9 publications

References 22 publications

Evaluation of antiviral drugs against newly emerged SARS-CoV-2 Omicron subvariants

Evaluation of antiviral drugs against newly emerged SARS-CoV-2 Omicron subvariants

An immunoinformatics approach to study the epitopes of SARS-CoV-2 helicase, Nsp13

A computational study on mitogenome-encoded proteins of Pavo cristatus and Pavo muticus identifies key genetic variations with functional implications

Contact Info

Product

Resources

About