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探索现有药物:提出治疗新冠肺炎的潜在化合物。

Exploring existing drugs: proposing potential compounds in the treatment of COVID-19.

作者信息

Kabir Eva Rahman, Mustafa Nashrah, Nausheen Nahid, Sharif Siam Mohammad Kawsar, Syed Easin Uddin

机构信息

Department of Pharmacy, Brac University, Bangladesh.

出版信息

Heliyon. 2021 Feb;7(2):e06284. doi: 10.1016/j.heliyon.2021.e06284. Epub 2021 Feb 25.

DOI:10.1016/j.heliyon.2021.e06284
PMID:33655082
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7906017/
Abstract

The COVID-19 situation had escalated into an unprecedented global crisis in just a few weeks. On the 30 of January 2020, World Health Organization officially declared the COVID-19 epidemic as a public health emergency of international concern. The confirmed cases were reported to exceed 105,856,046 globally, with the death toll of above 2,311,048, according to the dashboard from Johns Hopkins University on the 7 of February, 2021, though the actual figures may be much higher. Conserved regions of the South Asian strains were used to construct a phylogenetic tree to find evolutionary relationships among the novel virus. Off target similarities were searched with other microorganisms that have been previously reported using Basic Local Alignment Search Tool (BLAST). The conserved regions did not match with any previously reported microorganisms or viruses, which confirmed the novelty of SARS-CoV-2. Currently there is no approved drug for the prevention and treatment of COVID-19, but researchers globally are attempting to come up with one or more soon. Therapeutic strategies need to be addressed urgently to combat COVID-19. Successful drug repurposing is a tool that uses old and safe drugs, is time effective and requires lower development costs, and was thus considered for the study. Molecular docking was used for repurposing drugs from our own comprehensive database of approximately 300 highly characterized, existing drugs with known safety profile, to identify compounds that will inhibit the chosen molecular targets - SARS-CoV-2, ACE2, and TMPRSS2. The study has identified and proposed twenty seven candidates for further and studies for the treatment of SARS-CoV-2 infection.

摘要

在短短几周内,新冠疫情已升级为一场前所未有的全球危机。2020年1月30日,世界卫生组织正式宣布新冠疫情为国际关注的突发公共卫生事件。根据约翰·霍普金斯大学2021年2月7日的数据仪表盘,全球确诊病例报告超过1.05856046亿例,死亡人数超过231.1048万例,不过实际数字可能更高。利用南亚毒株的保守区域构建系统发育树,以找出这种新型病毒之间的进化关系。使用基本局部比对搜索工具(BLAST)与先前报道的其他微生物进行脱靶相似性搜索。这些保守区域与任何先前报道的微生物或病毒均不匹配,这证实了新冠病毒的新颖性。目前尚无批准用于预防和治疗新冠的药物,但全球研究人员正试图尽快研发出一种或多种药物。迫切需要制定治疗策略来对抗新冠疫情。成功的药物再利用是一种利用旧的安全药物的工具,具有时效性且开发成本较低,因此被纳入本研究。分子对接用于从我们自己包含约300种具有高度特征且已知安全性的现有药物的综合数据库中筛选可再利用的药物,以识别能够抑制所选分子靶点——新冠病毒、血管紧张素转换酶2(ACE2)和跨膜丝氨酸蛋白酶2(TMPRSS2)的化合物。该研究已确定并提出了27种候选药物,用于进一步研究治疗新冠病毒感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c48/7921819/822511091926/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c48/7921819/eae6ed72bd7b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c48/7921819/18eb59b349b4/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c48/7921819/822511091926/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c48/7921819/eae6ed72bd7b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c48/7921819/18eb59b349b4/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c48/7921819/822511091926/gr3.jpg

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