Protease inhibitors
Protease inhibitors (PIs) are promising candidates for antiviral agents. PIs can block the replication of viral genes via binding to enzymes that are responsible for proteolysis (Wu et al., 2004). Lopinavir and ritonavir, both protease inhibitors, have been approved as HIV medicines and have been found to possess antiviral activity against SARS and MERS. For the sake of destroying the SARS-CoV-2, clinical trials had begun to parse out the antiviral property of HIV protease inhibitors among patients. Notwithstanding, the antiviral effect of such inhibitors in coronavirus proteases remains controversial. Notably, a study regarding the comparison of the efficacy of prophylactic remdesivir and therapeutic remdesivir in combination with lopinavir, ritonavir, and interferon β against MERS-CoV unveiled that remdesivir was more effective than the combination therapy in reducing viral load and improving the degree of pathological changes in lung tissue. Aside from the gastrointestinal adverse reactions aroused by lopinavir/ritonavir, it is worth noting that lopinavir/ritonavir treatment alone may fail to offer benefits in comparison with standard care alone. The median time for clinical improvement was 16 days, and the reduction in viral RNA load among patients with severe SARS-CoV-2 did not appear to differ in both cases (B. Cao et al., 2020). Despite the disheartening outcomes, a marginally lower number of deaths were observed among the patients with lopinavir/ritonavir treatment in the late stage of this disease in contrast to the standard-care group. Further, Baden et al. suggested that the concentration of lopinavir/ritonavir required to inhibit the replication of SARS-CoV-2 in the lungs may be higher than the serum level (Baden and Rubin, 2020). Besides, nelfinavir, which is a selective inhibitor of HIV protease, has also been displayed to possess a robust suppression of SARS-CoV, indicating an alternative therapeutic option for COVID-19 (Yamamoto et al., 2004).