What are the main drugs under investigation that block SARS-CoV-2 replication?
Drugs designed to inhibit the viral replication machinery may be effective against SARS-CoV-2. For example, remdesivir inhibits viral RNA polymerases, which prevents SARS-CoV-2 replication. In a cohort of severe COVID-19 patients, compassionate-use of remdesivir showed clinical improvement in 68% of patients (36 out of 53).186 Of note, a double-blind, randomized, placebo-controlled trial of intravenous remdesivir was conducted in 1,063 adults hospitalized with COVID-19 with evidence of lower respiratory tract involvement; remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with COVID-19 and evidence of lower respiratory tract infection.187Furthermore, in a study of 5 HIV-positive hospitalized patients with severe COVID-19, 3 of them were given lopinavir-boosted ritonavir and 2 darunavir-boosted cobicistat for 14 days. Four patients recovered and 1 remained hospitalized.188 In another study with 99 hospitalized adult patients with severe COVID-19, no benefit beyond standard care was observed with lopinavir-boosted ritonavir treatment twice daily for 14 days.189 It is uncertain whether lopinavir-boosted ritonavir and other antiretrovirals improve clinical outcomes or prophylaxis among patients at high risk of SARS-CoV-2 infection.190 Additional potential candidates include other broad-spectrum antiviral drugs such as arbidol and favipiravir and phytochemicals with anti-viral activity such as resveratrol (Figure. 1 ).183