Abstract
The global spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes COVID-19 has become a source of grave medical and socioeconomic concern to human society. Since its first appearance in the Wuhan region of China in December 2019, the most effective measures of managing the spread of SARS-CoV-2 infection have been social distancing and lockdown of human activity; the level of which has not been seen in our generations. Effective control of the viral infection and COVID-19 will ultimately depend on the development of either a vaccine or therapeutic agents. This article highlights the progresses made so far in these strategies by assessing key targets associated with the viral replication cycle. The key viral proteins and enzymes that could be targeted by new and repurposed drugs are discussed.
Keywords: COVID-19, SARS-CoV-2, infection cycle, structural proteins, non-structural proteins, RNA dependent RNA polymerase, proteases, helicase, nucleosides.
Graphical Abstract
[http://dx.doi.org/10.1016/S1473-3099(20)30246-2] [PMID: 32243815]
[http://dx.doi.org/10.1073/pnas.96.24.13910] [PMID: 10570172]
[http://dx.doi.org/10.1016/j.apsb.2020.02.008] [PMID: 32292689]
[http://dx.doi.org/10.1016/S0140-6736(20)30251-8] [PMID: 32007145]
[http://dx.doi.org/10.1016/j.jmii.2020.03.022] [PMID: 32265180]
[http://dx.doi.org/10.1128/JVI.01052-08] [PMID: 18753196]
[http://dx.doi.org/10.1146/annurev-virology-110615-042301] [PMID: 27578435]
[http://dx.doi.org/10.1016/j.cell.2020.02.058] [PMID: 32155444]
[http://dx.doi.org/10.1186/s12985-019-1182-0] [PMID: 31133031]
[http://dx.doi.org/10.1016/S1473-3099(20)30134-1] [PMID: 32105641]
[http://dx.doi.org/10.1001/jama.2020.1585] [PMID: 32031570]
[http://dx.doi.org/10.1016/j.kint.2020.03.001] [PMID: 32204907]
[http://dx.doi.org/10.1038/nrmicro2090] [PMID: 19198616]
[http://dx.doi.org/10.1074/jbc.C300520200] [PMID: 14670965]
[http://dx.doi.org/10.1038/cr.2016.152] [PMID: 28008928]
[http://dx.doi.org/10.1016/0014-5793(89)80109-7] [PMID: 2645167]
[http://dx.doi.org/10.1016/j.lfs.2020.117477] [PMID: 32119961]
[http://dx.doi.org/10.1038/s41467-019-10280-3] [PMID: 31138817]
[http://dx.doi.org/10.1016/j.virusres.2017.01.023] [PMID: 28174054]
[http://dx.doi.org/10.1038/sj.emboj.7601368] [PMID: 17024178]
[http://dx.doi.org/10.1126/science.abb3405] [PMID: 32198291]
[http://dx.doi.org/10.1146/annurev.biochem.76.052305.115300] [PMID: 17506634]
[http://dx.doi.org/10.1093/nar/gkz409] [PMID: 31131400]
[http://dx.doi.org/10.20944/preprints202003.0085.v1]
[http://dx.doi.org/10.1128/JVI.02114-07] [PMID: 18094151]
[http://dx.doi.org/10.1038/nature17180] [PMID: 26934220]
[http://dx.doi.org/10.1136/gut.2005.076646] [PMID: 16905701]
[http://dx.doi.org/10.1016/j.antiviral.2006.05.014] [PMID: 16806515]
[http://dx.doi.org/10.2183/pjab.93.027] [PMID: 28769016]
[http://dx.doi.org/10.1007/s11901-010-0039-1] [PMID: 20461127]
[http://dx.doi.org/10.1016/j.bmcl.2003.10.067] [PMID: 14741291]
[http://dx.doi.org/10.3390/v7102868] [PMID: 26426038]
[http://dx.doi.org/10.1002/hep.22717] [PMID: 19072827]
[http://dx.doi.org/10.1128/AAC.01599-08] [PMID: 19307358]
[http://dx.doi.org/10.1128/AAC.05438-11] [PMID: 22143520]
[http://dx.doi.org/10.1016/j.jgg.2020.02.001] [PMID: 32173287]
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[http://dx.doi.org/10.1186/1743-422X-2-69] [PMID: 16115318]
[http://dx.doi.org/10.3390/molecules25081834] [PMID: 32316270]
[http://dx.doi.org/10.1371/journal.pone.0036521] [PMID: 22615777]
[http://dx.doi.org/10.1155/2011/213135] [PMID: 27516903]
[http://dx.doi.org/10.1016/j.chembiol.2005.01.006] [PMID: 15797214]
[http://dx.doi.org/10.1016/j.antiviral.2018.06.006] [PMID: 29885377]
[http://dx.doi.org/10.20944/preprints202003.0226.v1]
[http://dx.doi.org/10.1021/acsomega.8b03502]
[http://dx.doi.org/10.1039/C9TB00531E]