Repurposing Therapeutics for Potential Treatment of SARS-CoV-2: A Review

Abstract

<jats:p>The need for proven disease-specific treatments for the novel pandemic coronavirus SARS-CoV-2 necessitates a worldwide search for therapeutic options. Since the SARS-CoV-2 virus shares extensive homology with SARS-CoV and MERS-CoV, effective therapies for SARS-CoV and MERS-CoV may also have therapeutic potential for the current COVID-19 outbreak. To identify therapeutics that might be repositioned for treatment of the SARS-CoV-2 disease COVID-19, we strategically reviewed the literature to identify existing therapeutics with evidence of efficacy for the treatment of the three coronaviruses that cause severe respiratory illness (SARS-CoV, MERS-CoV, and SARS-CoV-2). Mechanistic and in vitro analyses suggest multiple promising therapeutic options with potential for repurposing to treat patients with COVID-19. Therapeutics with particularly high potential efficacy for repurposing include camostat mesylate, remdesivir, favipiravir, tocilizumab, baricitinib, convalescent plasma, and humanized monoclonal antibodies. Camostat mesylate has shown therapeutic potential, likely by preventing viral entry into epithelial cells. In early research, the targeted antivirals remdesivir and favipiravir appear to benefit patients by decreasing viral replication; clinical trials suggest that remdesivir speeds recovery from COVID-19. Tocilizumab and baricitinib appear to improve mortality by preventing a severe cytokine storm. Convalescent plasma and humanized monoclonal antibodies offer passive immunity and decreased recovery time. This review highlights potential therapeutic options that may be repurposed to treat COVID-19 and suggests opportunities for further research.</jats:p>

Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity

“…The SARS-CoV-2 isolate hCoV-19/Germany/FI1103201/2020 (GISAID accession EPI-ISL_463008) was isolated at the Institute of Virology, Muenster, Germany, from a patient returning from the Southern Tyrolean ski areas and propagated in Vero-TMPRSS2 cells. Calu-3 cells were pre-incubated for 2 h with 2-fold concentrated camostat mesylate or FOY-251 (2,20 or 200 µM), or DMSO (control), before they were inoculated with SARS-CoV-2 at an MOI of 0.001 or 0.01. For this, the identical volume of virus-containing medium was added to the inhibitor-containing medium on the cells (resulting in 1-fold concentrated camostat mesylate or FOY-251; 1, 10 or 100 µM).…”

“…The outbreak of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the city of Wuhan, China, in the winter of 2019 and its subsequent pandemic spread has resulted in more than 14 million cases of coronavirus disease 2019 and more than 600.00 deaths ( 1 ). Antivirals designed to combat SARS-CoV-2 are not available and repurposing of existing drugs developed against other diseases is considered the fastest option to close this gap ( 2 ). Remdesivir, a drug generated to inhibit Ebola virus infection, has recently been shown to reduce the duration of hospitalization for COVID-19 ( 3 ).…”

Current targets and drug candidates for prevention and treatment of SARS-CoV-2 (COVID-19) infection

“…Various drugs evaluated against SARS-CoV and MERS-CoV have been explored in terms of efficacy for repurposing during the SARS-CoV-2 outbreak (Horie et al, 2020;Kandimalla et al, 2020;Kalra et al, 2020;Pizzorno et al, 2020;Santos et al, 2020). Synthetic drugs (example chloroquine and hydroxychloroquine), and antivirals (remdesivir and favipiravir) and herbal phytoconstituents (baicalin, glycyrrhizin, hesperetin, quercetin, and scutellarin), are considered for COVID-19 due to their potential action on host ACE2 or RdRp (Chen et al, 2004;Ekins et al, 2020;Ho et al, 2007;Zhang and Yap, 2004).…”

Evaluation of the elemental, nutritional and antioxidant properties of Cov-Pla herbal preparations

“…A number of strategies are being pursued for the discovery of new therapeutics for the disease. These include repurposing of existing drugs (Santos et al, 2020), computer aided drug discovery (Onawole et al, 2020) and de novo synthesis and screening of small molecules against the SARS-CoV-2 virus (Ahmed-Belkacem et al, 2020;Jockusch et al, 2020). Another approach which is fast gaining traction for the discovery of new drugs against this disease is the exploration of plant material for herbal medicines against the disease (Cao et al, 2020;Wang et al, 2020).…”