Therapeutic strategies for COVID-19: progress and lessons learned

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic strategies that target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and/or human proteins to control viral infection, encompassing hundreds of potential drugs and thousands of patients in clinical trials. So far, a few small-molecule antiviral drugs (nirmatrelvir–ritonavir, remdesivir and molnupiravir) and 11 monoclonal antibodies have been marketed for the treatment of COVID-19, mostly requiring administration within 10 days of symptom onset. In addition, hospitalized patients with severe or critical COVID-19 may benefit from treatment with previously approved immunomodulatory drugs, including glucocorticoids such as dexamethasone, cytokine antagonists such as tocilizumab and Janus kinase inhibitors such as baricitinib. Here, we summarize progress with COVID-19 drug discovery, based on accumulated findings since the pandemic began and a comprehensive list of clinical and preclinical inhibitors with anti-coronavirus activities. We also discuss the lessons learned from COVID-19 and other infectious diseases with regard to drug repurposing strategies, pan-coronavirus drug targets, in vitro assays and animal models, and platform trial design for the development of therapeutics to tackle COVID-19, long COVID and pathogenic coronaviruses in future outbreaks.

Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies

“…In addition, SARS-CoV-2 RNA polymerase and protease inhibitors have been developed as small-molecule compounds. 1 Specific monoclonal antibodies with virus-neutralizing activity are another powerful approach for the treatment or prevention of SARS-CoV-2 infection. [2][3][4][5][6] SARS-CoV-2 antibody therapeutics demonstrating potent virus neutralization activity have been developed using monoclonal antibodies isolated from the B cells of patients with COVID-19.…”

Comparative Evaluation of RT-PCR Kits Available in Sri Lanka for Diagnosis of COVID-19

“…6 In addition to direct health consequences, the COVID-19 pandemic had a negative impact on the national economy, employment, tourism, poverty, exchange rate, social activity and welfare. 7 Although promising treatments like antigen neutralizing antibody treatments, which are able to provide long-term protection against COVID-19, 8,9 have been developed, their strict storage conditions, distribution requirements and high production costs limit accessibility of these treatment options for patients living in developing countries like Sri Lanka. 9 On the other hand, complete vaccination of the public will take time and investments and vaccines are not effective against emerging variants.…”

“…7 Although promising treatments like antigen neutralizing antibody treatments, which are able to provide long-term protection against COVID-19, 8,9 have been developed, their strict storage conditions, distribution requirements and high production costs limit accessibility of these treatment options for patients living in developing countries like Sri Lanka. 9 On the other hand, complete vaccination of the public will take time and investments and vaccines are not effective against emerging variants. 10 Therefore, early diagnosis and adequate preventive strategies are important to combat disease transmission.…”

Discovery of a novel inhibitor of macropinocytosis with antiviral activity

“…Although numerous drug-repurposing approaches have been reported, none have reached clinical practice 6 .…”