A comprehensive review on drug repositioning against coronavirus disease 2019 (COVID19)

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the reason for this ongoing pandemic infection diseases termed coronavirus disease 2019 (COVID-19) that has emerged since early December 2019 in Wuhan City, Hubei Province, China. In this century, it is the worst threat to international health and the economy. After 4 months of COVID-19 outbreak, there is no certain and approved medicine against it. In this public health emergency, it makes sense to investigate the possible effects of old drugs and find drug repositioning that is efficient, economical, and riskless process. Old drugs that may be effective are from different pharmacological categories, antimalarials, anthelmintics, anti-protozoal, anti-HIVs, anti-influenza, antihepacivirus, antineoplastics, neutralizing antibodies, immunoglobulins, and interferons. In vitro, in vivo, or preliminary trials of these drugs in the treatment of COVID-19 have been encouraging, leading to new research projects and trials to find the best drug/s. In this review, we discuss the possible mechanisms of these drugs against COVID-19. Also, it should be mentioned that in this manuscript, we discuss preliminary rationales; however, clinical trial evidence is needed to prove them. COVID-19 therapy must be based on expert clinical experience and published literature and guidelines from major health organizations. Moreover, herein, we describe current evidence that may be changed in the future.

Ebselen derivatives are very potent dual inhibitors of SARS-CoV-2 proteases - PLproand Mproin in vitro studies

“…Based on the screening results, we selected ebselen and seven of its derivatives for further inhibitory property evaluation. We chose compounds: a), exhibiting the highest potency towards M pro (10,17) or PL pro (7) in the screening assay; or b), displaying relatively high inhibition towards both the investigated proteases (3, 16, 20, 21) (Fig. 2).…”

“…This strategy can be supported by computational analysis, which can lower the costs, speed up the process in comparison with de-novo development of new therapeutics and serve as a first stage in screening vast libraries of active compound. [6][7][8][9][10] Drug repositioning has been already successfully used in fighting COVID-19. 11 A bright example here is remdesivir, an antiviral agent targeting viral RNA-dependent RNA polymerase (RdRp) that was designated to treat Ebola but has shown efficacy shortening recovery time and reducing mortality as well as serious adverse effects in COVID-19 patients.…”

Consideraciones sobre el diagnóstico de COVID-19 y el papel del diagnóstico salival

“…El brote inicial en un mercado local de mariscos en la ciudad de Wuhan, provincia de Hubei, en China a finales de diciembre del 2019, se ha extendido mundialmente, representando el mayor desafío sanitario en varias décadas, por lo que ha sido calificado por la Organización Mundial de la Salud (OMS) como una pandemia global desde el 11 de marzo del 2020. 1,3,4,6,[9][10][11][12][13] El 08 de enero del 2020, este nuevo coronavirus fue oficialmente anunciado como el patógeno causante de la COVID-19, por el centro chino para el control y prevención de la enfermedad (CDC, por sus siglas en inglés). 5 En el principio, se cree en el origen animal, y más tarde se demuestra la transmisión posible de persona a persona.…”

Molecular Features of Non-Selective Small Molecule Antagonists of the Bradykinin Receptors

“…Based on this novel mechanistic hypothesis, selective and non-selective BK antagonists should be considered as therapeutic agents for the treatment of covid-19 [26,27]. Despite the enormous effort devoted in the past to design peptide and non-peptide selective ligands targeting the BK receptors [13,28], icatibant (Figure 2) is the only BK antagonist presently approved as therapeutic agent for the symptomatic treatment of acute attacks of hereditary angioedema in adults with C1-esterase-inhibitor deficiency [29].…”