Abstract
The enigmatic coronavirus outburst on December 31, 2019, originated from Wuhan city of China, is now declared as Coronavirus Disease (COVID-19) by the World Health Organization (WHO). The causative agent is highly contagious, and its rapid blowout has affected almost every country of the world, endangering thousands of lives. Recently, the WHO has raised the COVID-19 epidemic threat to the “very high” level. Pathophysiological mechanisms are related to the inter-related functioning of various viral polyproteins, structural proteins as well as Non-Structural Proteins (NSP). These proteins play a crucial role in accelerating pathogenesis by promoting viral replication, viral assembly, and virion release, thereby disabling the overall host distinctive immunological system. Presently, there is no specific treatment for COVID-19. The majority of the treatments focus on symptomatic relief and supportive therapy only. Although several drugs have been investigated against coronavirus in numerous clinical trials, only a few exhibited mild-moderate signs of clinical recovery. Drugs that are being repurposed and researched include an anti-- malarial drug, hydroxychloroquine; anti-HIV drugs, lopinavir, Remdesivir alone, or in combination; anti-influenza drugs like umifenovir, and favilavir; anti-arthritic baracitinib, and anti-interleukins. Various research articles demonstrated the excellent potential of hydroxychloroquine either alone or in combination with anti-HIV drugs lopinavir, and Remdesivir at the cellular level; however, exhaustive clinical support and validation are still desirable for repurposing these drugs. Profound identification of cellular targets involved in disease pathogenesis may warrant successful re-profiling of the candidate drugs or their combinations aiming against COVID-19.
Keywords: Coronavirus, SARS-CoV-2, drug repurposing, pandemic, vaccines, convalescent plasma therapy, lopinavir, remdesivir, antiretrovirals, clinical trials.
Graphical Abstract
[http://dx.doi.org/10.1128/JCM.00187-20] [PMID: 32161092]
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105924] [PMID: 32081636]
[http://dx.doi.org/10.4103/ijp.IJP_115_20] [PMID: 32201449]
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[http://dx.doi.org/10.1146/annurev-micro-020518-115759] [PMID: 31226023]
[http://dx.doi.org/10.1016/S2213-2600(20)30161-2] [PMID: 32272080]
[http://dx.doi.org/10.1001/jama.2020.4031] [PMID: 32167538]
[http://dx.doi.org/10.1016/j.bbrc.2020.02.071] [PMID: 32081428]
[http://dx.doi.org/10.1002/jmv.25682] [PMID: 31967321]
[http://dx.doi.org/10.1016/B978-0-12-385885-6.00009-2] [PMID: 22094080]
[http://dx.doi.org/10.1016/j.jaut.2020.102433] [PMID: 32113704]
[http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143]
[http://dx.doi.org/10.1007/978-1-4939-2438-7_1] [PMID: 25720466]
[http://dx.doi.org/10.1016/j.cell.2020.04.011] [PMID: 32330414]
[http://dx.doi.org/10.24171/j.phrp.2020.11.1.02] [PMID: 32149036]
[http://dx.doi.org/10.1056/NEJMoa2001017] [PMID: 31978945]
[http://dx.doi.org/10.1128/MMBR.69.4.635-664.2005] [PMID: 16339739]
[http://dx.doi.org/10.1002/jmv.25719] [PMID: 32083328]
[http://dx.doi.org/10.1016/j.virusres.2007.02.017] [PMID: 17397959]
[http://dx.doi.org/10.1183/13993003.00607-2020] [PMID: 32269085]
[http://dx.doi.org/10.1016/S2213-2600(20)30076-X] [PMID: 32085846]
[http://dx.doi.org/10.1016/j.clim.2020.108427] [PMID: 32325252]
[http://dx.doi.org/10.1038/s41577-020-0311-8] [PMID: 32346093]
[http://dx.doi.org/10.3389/fmicb.2014.00296] [PMID: 24987391]
[http://dx.doi.org/10.1007/s00330-020-06827-4] [PMID: 32296940]
[http://dx.doi.org/10.1016/j.autrev.2020.102537] [PMID: 32251717]
[http://dx.doi.org/10.1126/science.abb8925] [PMID: 32303591]
[http://dx.doi.org/10.1016/j.immuni.2020.04.003] [PMID: 32325025]
[http://dx.doi.org/10.1016/j.clim.2020.108393] [PMID: 32222466]
[http://dx.doi.org/10.1016/j.jaut.2020.102452] [PMID: 32291137]
[http://dx.doi.org/10.3389/fimmu.2020.00827] [PMID: 32425950]
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105984] [PMID: 32305589]
[http://dx.doi.org/10.4155/fdd-2020-0010]
[http://dx.doi.org/10.1016/j.ijid.2020.02.018] [PMID: 32081774]
[http://dx.doi.org/10.31782/IJCRR.2020.12096]
[http://dx.doi.org/10.1001/archophthalmol.2011.321] [PMID: 22084231]
[http://dx.doi.org/10.1093/cid/ciaa237] [PMID: 32150618]
[http://dx.doi.org/10.1038/s41421-020-0156-0] [PMID: 32194981]
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105949] [PMID: 32205204]
[http://dx.doi.org/10.1016/j.ipej.2020.04.003] [PMID: 32278018]
[http://dx.doi.org/10.1016/j.medmal.2020.03.006] [PMID: 32240719]
[http://dx.doi.org/10.1136/bmj.m1849] [PMID: 32409561]
[http://dx.doi.org/10.1186/1743-422X-2-69] [PMID: 16115318]
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105938] [PMID: 32171740]
[http://dx.doi.org/10.1016/S0140-6736(20)31022-9] [PMID: 32423584]
[http://dx.doi.org/10.5812/archcid.13823]
[http://dx.doi.org/10.1038/s41467-019-13940-6] [PMID: 31924756]
[http://dx.doi.org/10.3346/jkms.2020.35.e79] [PMID: 32056407]
[http://dx.doi.org/10.1056/NEJMoa2001282] [PMID: 32187464]
[http://dx.doi.org/10.1101/2020.03.07.982264] [PMID: 32511335]
[http://dx.doi.org/10.1007/s12519-020-00344-6] [PMID: 32026147]
[http://dx.doi.org/10.3390/ph13040065] [PMID: 32290348]
[http://dx.doi.org/10.1016/j.antiviral.2020.104791] [PMID: 32275914]
[http://dx.doi.org/10.2139/ssrn.3569866]
[http://dx.doi.org/10.1073/pnas.1617020114] [PMID: 28003465]
[http://dx.doi.org/10.1093/cid/ciaa272] [PMID: 32176772]
[http://dx.doi.org/10.2183/pjab.93.027] [PMID: 28769016]
[http://dx.doi.org/10.1128/AAC.49.3.981-986.2005] [PMID: 15728892]
[http://dx.doi.org/10.1016/j.eng.2020.03.007] [PMID: 32346491]
[http://dx.doi.org/10.1002/cpt.1844] [PMID: 32246834]
[http://dx.doi.org/10.33945/SAMI/AJCB.2020.2.3]
[http://dx.doi.org/10.1016/j.antiviral.2020.104787] [PMID: 32251768]
[http://dx.doi.org/10.4269/ajtmh.20-0271] [PMID: 32314704]
[http://dx.doi.org/10.1007/s40261-020-00917-3] [PMID: 32337664]
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105954] [PMID: 32234467]
[http://dx.doi.org/10.1002/jmv.25801] [PMID: 32253759]
[http://dx.doi.org/10.1073/pnas.2005615117] [PMID: 32350134]
[http://dx.doi.org/10.1007/s11739-020-02345-9] [PMID: 32347443]
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[http://dx.doi.org/10.1016/S0140-6736(20)30304-4] [PMID: 32032529]
[http://dx.doi.org/10.1016/S1473-3099(20)30132-8] [PMID: 32113509]
[http://dx.doi.org/10.1038/s41586-018-0774-y] [PMID: 30542164]
[http://dx.doi.org/10.1016/S1473-3099(20)30141-9] [PMID: 32113510]
[http://dx.doi.org/10.1172/JCI138745] [PMID: 32254064]
[http://dx.doi.org/10.1136/jnnp-2020-323586] [PMID: 32354768]
[http://dx.doi.org/10.1016/S0140-6736(20)30566-3] [PMID: 32171076]
[http://dx.doi.org/10.1148/radiol.2020201629] [PMID: 32324101]
[http://dx.doi.org/10.7326/M20-2003] [PMID: 32374815]
[http://dx.doi.org/10.1111/jth.14817] [PMID: 32220112]
[http://dx.doi.org/10.1136/bmj.m2648] [PMID: 32620554]
[http://dx.doi.org/10.1136/bmj.m2422] [PMID: 32546467]
[http://dx.doi.org/10.1016/j.tips.2020.03.006] [PMID: 32291112]
[http://dx.doi.org/10.1016/S2589-7500(20)30086-8] [PMID: 32363333]
[http://dx.doi.org/10.1007/s40475-020-00201-6] [PMID: 32219057]
[http://dx.doi.org/10.1038/d41573-020-00073-5] [PMID: 32273591]
[http://dx.doi.org/10.1016/j.immuni.2020.03.007] [PMID: 32259480]