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. 2020 Dec 1;28(23):115757.
doi: 10.1016/j.bmc.2020.115757. Epub 2020 Sep 10.

COVID-19 therapy: What weapons do we bring into battle?

Sinara Mônica Vitalino de Almeida  1 , José Cleberson Santos Soares  2 , Keriolaine Lima Dos Santos  2 , Josival Emanuel Ferreira Alves  3 , Amélia Galdino Ribeiro  2 , Íris Trindade Tenório Jacob  2 , Cindy Juliane da Silva Ferreira  4 , Jéssica Celerino Dos Santos  4 , Jamerson Ferreira de Oliveira  2 , Luiz Bezerra de Carvalho Junior  3 , Maria do Carmo Alves de Lima  2
Affiliations

COVID-19 therapy: What weapons do we bring into battle?

Sinara Mônica Vitalino de Almeida et al. Bioorg Med Chem. .

Abstract

Urgent treatments, in any modality, to fight SARS-CoV-2 infections are desired by society in general, by health professionals, by Estate-leaders and, mainly, by the scientific community, because one thing is certain amidst the numerous uncertainties regarding COVID-19: knowledge is the means to discover or to produce an effective treatment against this global disease. Scientists from several areas in the world are still committed to this mission, as shown by the accelerated scientific production in the first half of 2020 with over 25,000 published articles related to the new coronavirus. Three great lines of publications related to COVID-19 were identified for building this article: The first refers to knowledge production concerning the virus and pathophysiology of COVID-19; the second regards efforts to produce vaccines against SARS-CoV-2 at a speed without precedent in the history of science; the third comprehends the attempts to find a marketed drug that can be used to treat COVID-19 by drug repurposing. In this review, the drugs that have been repurposed so far are grouped according to their chemical class. Their structures will be presented to provide better understanding of their structural similarities and possible correlations with mechanisms of actions. This can help identifying anti-SARS-CoV-2 promising therapeutic agents.

Keywords: Antiviral; COVID-19; Coronavirus; Repurposed drugs; SARS-CoV-2.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
SARS-CoV-2 life cycle and putative therapeutic _targets. SARS-CoV-2 life cycle starts with the activation of protein S and link to the angiotensin-converting enzyme 2 (ACE2) receptor. After host cell entrance by via endosomal, SARS-CoV-2 releases the RNA into the cytoplasm to be translated into viral replicase polyproteins including proteases (3CLpro and PLpro), which cleavage products (nonstructural proteins- Nsps) form the transcription and replication complex. The positive RNA strand is translated into a template of negative strand that allows the synthesis of new genomics and sub genomics mRNAs. These mRNAs are translated and transcribed producing structural and accessory proteins. Next, the virions are prepared at endoplasmic reticulum and Golgi complex, transported through vesicles and finally released by exocytosis. The structures of some promising therapeutic _targets available on Protein Data Bank are: (a) SARS-CoV-2 Spike glycoprotein (PDB ID 6VXX); (b) SARS-CoV-2 spike receptor-binding domain bound with ACE2 (PDB ID 6M0J); (c) Native Human ACE2 (PDB ID 1R42); (d) papain-like protease (PLpro) of SARS CoV-2 (PDB ID 6W9C); (e) structure of COVID-19 main protease (Mpro) in complex with an inhibitor N3 (PDB ID 6LU7); (f) SARS-Cov-2 RdRp in complex with cofactors (PDB ID 6 M71). Figure created with biorender.com.
Fig. 2
Fig. 2
Chemical structure of proteinase 3CLpro inhibitors: N3 (1); Ebselen (2); PX-12 (3) and Carmofur (4).
Fig. 3
Fig. 3
Chemical structures of pyrimidine nitrogenous bases cytosine (5), uracil (6) and thymine (7) and pyrimidine derivatives drugs: 5-Fluorouracil (8); Gemcitabine (9); Baricitinib (10); Sunitinib (11); Erlotinib (12); Galidesivir (13); Sofosbuvir (14); Telbivudine (15).
Fig. 4
Fig. 4
Chemical structures of purine nitrogenous bases adenine (16) and guanine (17) and others nitrogen-based analogue drugs: Remdesivir (18); Ganciclovir (19); Valganciclovir (20); Tenofovir (21); Ribavirin (22); Favipiravir (23).
Fig. 5
Fig. 5
Chemical structures of peptide derivatives, amino acids and analogues drugs: Lopinavir (24); Ritonavir (25); Oseltamivir (26); Nelfinavir (27); Atazanavir (28); Captopril (29); Ciclosporin A (30), Teicoplanin (31).
Fig. 6
Fig. 6
Chemical structures of Dasabuvir (32), Darunavir (33), Dasatinib (34), Imatinib (35) and Nitazoxanide (36) drugs.
Fig. 7
Fig. 7
Chemical structures of quinolines, macrolides and indole derivatives drugs: Chloroquine (37); Hydroxychloroquine (38); Ivermectin (39); Arbidol (40); Rizatriptan (41); Melatonin (42).
Fig. 8
Fig. 8
Chemical structures of alkaloids and derivatives, glycopeptides, amides, peptidomimetics and steroid derivatives drugs: Emetine (43); Homoharringtonine (44); Disulfiram (45); Dexamethasone (46).
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