Coronaviruses (CoVs) are a large family of viruses responsible for the severe pathophysiological effects on human health. The most severe outbreak includes Severe Acute Respiratory Syndrome (SARS-CoV), Middle East Respiratory Syndrome (MERS-CoV) and Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 poses major challenges to clinical management because no specific FDA-approved therapy yet to be available. Thus, the existing therapies are being used for the treatment of COVID-19, which are under clinical trials and compassionate use, based on in vitro and in silico studies. In this review, we summarize the potential therapies utilizing small molecules, bioactive compounds, nucleoside and nucleotide analogs, peptides, antibodies, natural products, and synthetic compounds targeting the complex molecular signaling network involved in COVID-19. In this review＞230 natural and chemically synthesized drug therapies are described with their recent advances in research and development being done in terms of their chemical, structural and functional properties. This review focuses on possible targets for viral cells, viral proteins, viral replication, and different molecular pathways for the discovery of novel viral- and host-based therapeutic targets against SARS-CoV-2.
Keywords: Therapeutic drugs, Natural compounds, Viral inhibitors, SARS-CoV-2, COVID-19
Abbreviations: COVID-19, Coronavirus disease 2019; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; MERS, Middle East respiratory syndrome; HCoV, human coronavirus; CHIKV, Chikungunya virus; DHODH, dihydroorotate dehydrogenase; HBV, hepatitis B virus; IAV, influenza A virus; HCV, hepatitis C virus; JEV, Japanese encephalitis virus; PEDV, porcine epidemic diarrhea virus; PLpro, papain-like protease; 3CLpro, 3 chymotrypsin-like proteases; RdRp, RNA-dependent RNA polymerase; SAH, S-adenosyl-l-homocysteine; RBD, receptor-binding domain; RSV, respiratory syncytial virus; ZIKV, Zika virus; IMPDH, inosine-monophosphate dehydrogenase; PPIase, peptidyl-prolyl isomerase; IMPTH, inosine-5′-monophosphate dehydrogenase; NS3, non-structural protein 3; VEGF, Vascular Endothelial Growth Factor; ALI, acute lung injury; ARDS, acute respiratory distress syndrome; HTCC, N-(2hydroxypropyl)-3-trimethylammoniumchitosan chloride; SCV, SARS-associated coronavirus; HCMV, Human cytomegalovirus; COX, cyclooxygenase; JAK, Janus-associated kinase; NAK, Numb-associated kinase; HCMV, Human Cytomegalovirus; NS, Not studied; S protein, Spike (S) protein; E, Enveloped protein; ACE2, angiotensin-converting enzyme 2 (ACE2) blockers; TCM, traditional Chinese medicine
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