Understanding the binding mechanism for potential inhibition of SARS-CoV-2 Mpro and exploring the modes of ACE2 inhibition by hydroxychloroquine


Posted: 2021-11-06 19:00:00
J Cell Biochem . 2021 Nov 6. doi: 10.1002/jcb.30174. Online ahead of print. Affiliations Expand Affiliations 1 Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Maharashtra, India. 2 CAS in Crystallography and Biophysics, University of Madras, Chennai, Tamil Nadu, India. 3 Bioinformatics Infrastructure Facility, College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, Assam, India. Item in Clipboard Manisha Choudhury et al. J Cell Biochem. 2021. Show details Display options Display options Format J Cell Biochem . 2021 Nov 6. doi: 10.1002/jcb.30174. Online ahead of print. Affiliations 1 Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Maharashtra, India. 2 CAS in Crystallography and Biophysics, University of Madras, Chennai, Tamil Nadu, India. 3 Bioinformatics Infrastructure Facility, College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, Assam, India. Item in Clipboard CiteDisplay options Display options Format Abstract As per the World Health Organization report, around 226 844 344 confirmed positive cases and 4 666 334 deaths are reported till September 17, 2021 due to the recent viral outbreak. A novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) is responsible for the associated coronavirus disease (COVID-19), which causes serious or even fatal respiratory tract infection and yet no approved therapeutics or effective treatment is currently available to combat the outbreak. Due to the emergency, the drug repurposing approach is being explored for COVID-19. In this study, we attempt to understand the potential mechanism and also the effect of the approved antiviral drugs against the SARS-CoV-2 main protease (Mpro). To understand the mechanism of inhibition of the malaria drug hydroxychloroquine (HCQ) against SARS-CoV-2, we performed molecular interaction studies. The studies revealed that HCQ docked at the active site of the Human ACE2 receptor as a possible way of inhibition. Our in silico analysis revealed that the three drugs Lopinavir, Ritonavir, and Remdesivir showed interaction with the active site residues of Mpro. During molecular dynamics simulation, based on the binding free energy contributions, Lopinavir showed better results than Ritonavir and Remdesivir. Keywords: ACE-2; Lopinavir; Mpro; Ritonavir; SARS-CoV-2; hydroxychloroquine. © 2021 Wiley Periodicals LLC. References REFERENCES Hui DS, Azhar I, Madani E, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health: the latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020;91:264-266. doi:10.1016/j.ijid.2020.01.009 Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-271. doi:10.1038/s41422-020-0282-0 Hodos RA, Kidd BA, Shameer K, Readhead BP, Dudley JT. In silico methods for drug repurposing and pharmacology. WIREs: Sys Biol Med. 2016;8(3):186-210. doi:10.1002/wsbm.1337 Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet. 2015;385(9979):1729-1737. doi:10.1016/S0140-6736(14)62449-1 Wang Y, Lv Z, Chu Y. HIV protease inhibitors: a review of molecular selectivity and toxicity. HIV AIDS (Auckl). 2015;7:95-104. doi:10.2147/HIV.S79956 Show all 44 references [x] Cite Copy Format: Send To [x]

参考サイト PubMed: covid-19



バイオクイックニュース日本語版:COVID-19特集

バイオクイックニュース日本語版
6月 10, 2020 バイオアソシエイツ

新型コロナウイルスSARS-CoV-2は、本当は血管疾患かもしれない

最初は肺炎の形で肺に大きく影響すると考えられていた COVID-19 だが、2020年4月にCOVID-19に起因する多くの謎の症状の1つとして血栓が浮上した。 この直後、コロナウイルス関連の脳卒中が原因で若者が亡くなったという報告が出され、その次に、COVIDつま先という、痛みを伴う赤または紫の指が報告された。これらの症状のすべてに共通するものは何か? 血液循環の障害だ。…

ゲスト 717人 と メンバー 6人 がオンラインです