Potential therapeutic target identification in the novel 2019 coronavirus: insight from homology modeling and blind docking study

• Published in: Egyptian Journal of Medical Human Genetics 2020-10, Vol.21 (1), p.44-17
• Main Authors: Durojaye, Olanrewaju Ayodeji, Mushiana, Talifhani, Uzoeto, Henrietta Onyinye, Cosmas, Samuel, Udowo, Victor Malachy, Osotuyi, Abayomi Gaius, Ibiang, Glory Omini
• Format: Article
• Language: English
• Subjects: Amino acid sequence; Binding sites; Computer applications; Coronaviridae; Coronavirus; Coronavirus infections; Coronaviruses; COVID-19; Cytotoxicity; Genomes; Genomics; Health aspects; HIV; Homology; Human immunodeficiency virus; Inhibitors; Ligand; Nucleotide sequence; Polyproteins; Protease inhibitors; Proteases; Protein binding; Protein structure; Proteinase; Proteinase inhibitors; Proteins; Proteolysis; Public health; Replication; RNA; RNA viruses; Therapeutic targets; Viral infections
• ISSN: 1110-8630; 2090-2441
• DOI: 10.1186/s43042-020-00081-5

Background The 2019-nCoV which is regarded as a novel coronavirus is a positive-sense single-stranded RNA virus. It is infectious to humans and is the cause of the ongoing coronavirus outbreak which has elicited an emergency in public health and a call for immediate international concern has been linked to it. The coronavirus main proteinase which is also known as the 3C-like protease (3CLpro) is a very important protein in all coronaviruses for the role it plays in the replication of the virus and the proteolytic processing of the viral polyproteins. The resultant cytotoxic effect which is a product of consistent viral replication and proteolytic processing of polyproteins can be greatly reduced through the inhibition of the viral main proteinase activities. This makes the 3C-like protease of the coronavirus a potential and promising target for therapeutic agents against the viral infection. Results This study describes the detailed computational process by which the 2019-nCoV main proteinase coding sequence was mapped out from the viral full genome, translated and the resultant amino acid sequence used in modeling the protein 3D structure. Comparative physiochemical studies were carried out on the resultant target protein and its template while selected HIV protease inhibitors were docked against the protein binding sites which contained no co-crystallized ligand. Conclusion In line with results from this study which has shown great consistency with other scientific findings on coronaviruses, we recommend the administration of the selected HIV protease inhibitors as first-line therapeutic agents for the treatment of the current coronavirus epidemic.