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).