مبنای ساختاری کشف دارو
Abstract
Graphical abstract
۱٫ Introduction
۲٫ Materials and methods
۳٫ Results and discussion
۴٫ Conclusion
Declaration of competing interest
Acknowledgements
Appendix A. Supplementary data
Research Data
References
Abstract
The recent outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in December 2019 raised global health concerns. The viral 3-chymotrypsin-like cysteine protease (3CLpro) enzyme controls coronavirus replication and is essential for its life cycle. 3CLpro is a proven drug discovery target in the case of severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). Recent studies revealed that the genome sequence of SARS-CoV-2 is very similar to that of SARS-CoV. Therefore, herein, we analysed the 3CLpro sequence, constructed its 3D homology model, and screened it against a medicinal plant library containing 32,297 potential anti-viral phytochemicals/traditional Chinese medicinal compounds. Our analyses revealed that the top nine hits might serve as potential anti- SARS-CoV-2 lead molecules for further optimisation and drug development process to combat COVID-19.
Introduction
The first case of the novel coronavirus was reported on December 30, 2019, in Wuhan city, Hubei province, P.R. China [1]. Swift actions were taken by the Centre for Disease Control and Prevention (CDC), Chinese health authorities, and researchers. The World Health Organization (WHO) temporarily named this pathogen 2019 novel coronavirus (2019-nCoV) [2]. On January 10, 2020, the first whole-genome sequence of 2019-nCoV was released, which helped researchers to quickly identify the virus in patients using reverse-transcription polymerase chain reaction (RT-PCR) methods [3]. On January 21, the first article related to 2019-nCoV was published, which revealed that 2019-nCoV belongs to the beta-coronavirus group, sharing ancestry with bat coronavirus HKU9-1, similar to SARS-coronaviruses, and despite sequence diversity its spike protein interacts strongly with the human ACE2 receptor [1]. On January 30, the WHO announced a Public Health Emergency of International Concern (PHEIC) for the 2019-nCoV outbreak. Later, the human-to-human transmission was confirmed. As of January 31, 51 whole-genome sequences of 2019-nCoV from different laboratories and regions have been submitted to GISAID database [4]. On the February 12 th , the WHO permanently named the 2019-nCoV pathogen as SARS-CoV-2 and the causing disease as coronavirus disease 2019 (COVID-2019). Chinese government swift actions helped them to control COVID-19 in China. However, SARS-CoV-2 quickly spread to over 150 countries. On March 11th , WHO formally recognized the COVID-19 as a pandemic. By March 19th , 2020, the global death toll reached to 9,913, with 2,42,650 laboratory-confirmed cases. The case fatality rate among infected people is varying in different countries. However, global case fatality rate is presently around 3.92% (calculated as deaths / [deaths + laboratory confirmed cases]).