Dataset Information

Exploring RdRp-remdesivir interactions to screen RdRp inhibitors for the management of novel coronavirus 2019-nCoV.

ABSTRACT: A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has resulted in an increasing number of patients globally, and has become a highly lethal pathogenic member of the coronavirus family affecting humans. 2019-nCoV has established itself as one of the most threatening pandemics that human beings have faced, and therefore analysis and evaluation of all possible responses against infection is required. One such strategy includes utilizing the knowledge gained from the SARS and MERS outbreaks regarding existing antivirals. Indicating a potential for success, one of the drugs, remdesivir, under repurposing studies, has shown positive results in initial clinical studies. Therefore, in the current work, the authors have attempted to utilize the remdesivir-RdRp complex - RdRp (RNA-dependent RNA polymerase) being the putative target for remdesivir - to screen a library of the already reported RdRp inhibitor database. Further clustering on the basis of structural features and scoring refinement was performed to filter out false positive hits. Finally, molecular dynamics simulation was carried out to validate the identification of hits as RdRp inhibitors against novel coronavirus 2019-nCoV. The results yielded two putative hits which can inhibit RdRp with better potency than remdesivir, subject to further biological evaluation.

SUBMITTER: Singh PK

PROVIDER: S-EPMC7597014 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV.

Dataset Information

Exploring RdRp-remdesivir interactions to screen RdRp inhibitors for the management of novel coronavirus 2019-nCoV.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets