Target-based drug discovery, ADMET profiling and bioactivity studies of antibiotics as potential inhibitors of SARS-CoV-2 main protease (Mpro)

被引：43

作者：

Abdul-Hammed M. ^{[1
]}

Adedotun I.O. ^{[1
]}

Falade V.A. ^{[1
]}

Adepoju A.J. ^{[1
]}

Olasupo S.B. ^{[3
]}

Akinboade M.W. ^{[2
]}

机构：

[1] Department of Pure and Applied Chemistry, Ladoke Akintola University of Technology, P.M.B. 4000, Ogbomoso

[2] Department of Biochemistry, Ladoke Akintola University of Technology, P.M.B. 4000, Ogbomoso

[3] National Agency for Food and Drug Administration and Control (NAFDAC), Abuja

来源：

VirusDisease | 2021年 / 32卷 / 4期

关键词：

ADMET profiling; Antibiotics; COVID-19; Molecular docking; SARS-CoV-2 main protease (M[!sup]pro[!/sup]);

D O I：

10.1007/s13337-021-00717-z

中图分类号：

学科分类号：

摘要：

A recent outbreak of a new strain of Coronavirus (SARS-CoV-2) has become a global health burden, which has resulted in deaths. No proven drug has been found to effectively cure this fast-spreading infection, hence the need to explore old drugs with the known profile in tackling this pandemic. A computer-aided drug design approach involving virtual screening was used to obtain the binding scores and inhibiting efficiencies of previously known antibiotics against SARS-CoV-2 main protease (Mpro). The drug-likeness analysis of the repurposed drugs were done using the Molinspiration chemoinformatics tool, while the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis was carried out using ADMET SAR-2 webserver. Other analyses performed include bioactivities of the repurposed drug as a probable anti-SARS-CoV-2 agent and oral bioavailability analyses among others. The results were compared with those of drugs currently involved in clinical trials in the ongoing pandemic. Although antibiotics have been speculated to be of no use in the treatment of viral infections, literature has emerged lately to reveal the antiviral potential and immune-boosting ability of antibiotics. This study identified Tarivid and Ciprofloxacin with binding affinities of − 8.3 kcal/mol and − 8.1 kcal/mol, respectively as significant inhibitors of SARS-CoV-2 (Mpro) with better pharmacokinetics, drug-likeness and oral bioavailability, bioactivity properties, ADMET properties and inhibitory strength compared to Remdesivir (− 7.6 kcal/mol) and Azithromycin (− 6.3 kcal/mol). These observations will provide insight for further research (clinical trial) in the cure and management of COVID-19. © 2021, Indian Virological Society.

引用

页码：642 / 656

页数：14

共 60 条

[1]

Abdul-Hammed M., Adedotun I.O., Olajide M., Irabor C.O., Afolabi T.I., Gbadebo I.O., Rhyman L., Ramasami P., Virtual screening, ADMET profiling, PASS prediction, and bioactivity studies of potential inhibitory roles of alkaloids, phytosterols, and flavonoids against COVID-19 main protease (Mpro), Natl Prod Res, (2021)

[2]

Adedeji W.A., The treasure called antibiotics, Ann Ibadan Postgrad Med, 14, pp. 56-57, (2016)

[3]

Bergenhem N., Preclinical candidate nomination and development, Admet for medicinal chemists, pp. 399-415, (2011)

[4]

Biovia DS Discovery Studio Modeling Environment, (2015)

[5]

Bohacek R.S., Mcmartin C., Guida W.C., The art and practice of structure-based drug design: a molecular modeling perspective, Med Res Rev, 16, pp. 3-50, (1996)

[6]

Burlingham B.T., Widlanski T.S., An intuitive look at the relationship of Ki and IC50: a more general use for the dixon plot, J Chem Educ, 80, pp. 214-218, (2003)

[7]

Cals J.W.L., Boumans D., Lardinois R.J.M., Gonzales R., Hopstaken R.M., Butler C.C., Dinant G.J., Public beliefs on antibiotics and respiratory tract infections: an internet-based questionnaire study, Br J Gen Pract, 57, pp. 942-947, (2007)

[8]

Caly L., Druce J.D., Catton M.G., Jans D.A., Wagsta K.M., The FDA-approved drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Res, 178, (2020)

[9]

Carlet J., Collignon P., Goldmann D., Gyssens I.C., Harbarth S., Jarlier V., Levy S.B., N'Doye B., Pittet D., Richtmann R., Seto W.H., van der Meer J.W., Voss A., Society’s failure to protect a precious resource: antibiotics, Lancet, 378, pp. 369-371, (2011)

[10]

Chan J.F., Yuan S., Kok K.H., Yuan S., Kai K., Chu H., Yang J., Xing F., Liu J., Yip C.C., Poon R.W., Tsoi H., Lo S.K., Chan K., Poon V.K., Chan W., Ip J.D., Cai J., Cheng V.C., Chen H., Hui C.K., Yuen K., A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster, Lancet, 395, pp. 514-523, (2020)

← 1 2 3 4 5 6 →