Sequence : Nsp13 |
Total row(s): 2 |
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Most frequent and prevalent mutation reported, with reference to Wuhan sequence (hCoV-19/Wuhan/WIV04/2019), was P323L in the non-structural protein 12 (94.7%) whereas the second frequent mutation was D614G in the Spike glycoprotein region (92.6%), followed by G71S in the non-structural protein 5 (70%). | SARS-CoV-2 Genome sequences generated in the study (Refer Supplementary Table 1 and 2) | (Int J Infect Dis)
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Compared to the SARS-CoV-2 reference genome (MN908947.3), the SARS-CoV-2 isolate, CHRF_nCoV19_0001/Bangladesh (accession number: MT476385), was observed to have nine mutations. | | (Microbiol Resour Announc)
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Structure : Nsp13 |
Total row(s): 2 |
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Structure of SARS-CoV-2 mini RTC assembly by viral RNA-dependent RNA polymerase (nsp12) with a template-primer RNA, nsp7 and nsp8, and two helicase molecules (nsp13-1 and nsp13-2). nsp13-1 stabilizes the mini RTC by contacting with nsp13-2, which anchors the 5'-extension of RNA template, and interacts with nsp7-nsp8-nsp12-RNA. | | (Nat Commun)
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Structural characterisation of SARS-CoV-2 mini replication and transcription complex | | (Nat Commun)
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Drugs : Nsp13 |
Total row(s): 4 |
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Virtual screening of 970 000 chemical compounds against the ATP-binding site to identify potential inhibitors indicates two of the top drug hits (Cepharanthine,Lumacaftor) have significant activity in inhibiting purified recombinant SARS-CoV-2 helicase. | ATPase activity was performed to validate high throughput virtual screening method. | (J Phys Chem Lett)
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In-silico models of Nsp13 helicase and nsp14 were generated using comparative homology modelling. The structures were validated and then used for virtual screening of pre-existing, FDA approved antiviral drugs.This was done to verify that these drugs could be repurposed to be used against SARS-CoV-2 infection. | | (Gene Rep)
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In the present study, the in silico models of SARS-CoV-2 nsp13 helicase and nsp14 protein were elucidated using a comparative homology modelling approach. Simeprevir (SMV), Paritaprevir (PTV) and Grazoprevir (GZR) were the common leads identified which show higher binding affinity to both nsp13 helicase and nsp14 as compared to the control inhibitors and therefore, they might be potential dual-target inhibitors. | | (Gene Rep)
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The in silico models were further used for virtual screening of the Food and Drug Administration (FDA) approved antiviral drugs. Simeprevir (SMV), Paritaprevir (PTV) and Grazoprevir (GZR) were the common leads identified which show higher binding affinity to both nsp13 helicase and nsp14 as compared to the control inhibitors and therefore, they might be potential dual-target inhibitors. | | (Gene Rep)
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Molecular_interactions : Nsp13 |
Total row(s): 1 |
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Nsp13-1 stabilizes SARS-CoV-2 replication and transcription (RTC) complex by contacting with nsp13-2, which anchors the 5'-extension of RNA template, and interacting with nsp7-nsp8-nsp12-RNA. Different orientations of nsp13-1 results in different interactions with the two forms of mini RTC. | Mini RTC with an nsp12R365A mutation has greater helicase activity compared to individual apsnsp13. Nsp13-1T216A mutation has a decreased helicase activity. | (Nat Commun)
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