J Korean Med Sci.  2024 Apr;39(14):e134. 10.3346/jkms.2024.39.e134.

Review of COVID-19 Therapeutics by Mechanism: From Discovery to Approval

• Choi HS
• Choi AY
• Kopp JB
• Winkler CA
• Cho SK

• KMID: 2554586
• DOI: http://doi.org/10.3346/jkms.2024.39.e134

Abstract

The global research and pharmaceutical community rapidly mobilized to develop treatments for coronavirus disease 2019 (COVID-19). Existing treatments have been repurposed and new drugs have emerged. Here we summarize mechanisms and clinical trials of COVID-19 therapeutics approved or in development. Two reviewers, working independently, reviewed published data for approved COVID-19 vaccines and drugs, as well as developmental pipelines, using databases from the following organizations: United States Food and Drug Administration (US-FDA), European Medicines Agency (EMA), Japanese Pharmaceutical and Medical Devices Agency (PMDA), and ClinicalTrials.gov. In all, 387 drugs were found for initial review. After removing unrelated trials and drugs, 66 drugs were selected, including 17 approved drugs and 49 drugs under development. These drugs were classified into six categories: 1) drugs targeting the viral life cycle 2) Anti-severe acute respiratory syndrome coronavirus 2 Monoclonal Antibodies, 3) immunomodulators, 4) anti-coagulants, 5) COVID-19-induced neuropathy drugs, and 6) other therapeutics. Among the 49 drugs under development are the following: 6 drugs targeting the viral life cycle, 12 immunosuppression drugs, 2 immunostimulants, 2 HIF-PHD targeting drugs, 3 GM-CSF targeting drugs, 5 anti-coagulants, 2 COVID-19-induced neuropathy drugs, and 17 others. This review provides insight into mechanisms of action, properties, and indications for COVID-19 medications.

Keyword

COVID-19; SARS-CoV-2; Clinical Trials; Review

Figure

• 

  Fig. 1 Flow chart showing the review process for selection of publications to be reviewed.COVID-19 = coronavirus disease 2019, FDA = US Food and Drug Administration, EMA = European Medicines Agency, PMDA = Japanese Pharmaceutical and Medical Devices Agency, HIF-PHD = hypoxia-inducible factor prolyl hydroxylase, GM-CSF = granulocyte-macrophage colony-stimulating factor.

• 

  Fig. 2 SARS-CoV-2 life cycle. Medications in black font are approved. Medications in blue font are under development.ER = endoplasmic reticulum.

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  Fig. 3 Immune modulators used in COVID-19 treatment. Medications written in black are approved and medications written in blue are under development. Gray boxes denote medications that are immunostimulants. Yellow boxes denote medications that are immunosuppressants.JAK = Janus kinase, IL = interleukin.

• 

  Fig. 4 Blood coagulation and anticoagulation pathways and related drugs. Therapies are shown in white boxes.SYK = spleen tyrosine kinase.

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  Fig. 5 Hypoxia-inducible factor-prolyl hydroxylase (HIF-PHD) pathway and its related drugs.HIF = hypoxia-inducible factor, PHD = prolyl hydroxylase, VEGF = vascular endothelial growth factor.

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