Role of Chloroquine and Hydroxychloroquine in the Treatment of COVID-19 Infection- A Systematic Literature Review

Krishan Mohan Kapoor; Aanandita Kapoor

CQ inhibits the virus replication by reducing the terminal glycosylation of angiotensin-converting enzyme 2 (ACE2) receptors on the Vero E6 cells' surface and interfering with the binding of SARS-CoV to the ACE2 receptors. CQ had a significant inhibitory antiviral effect when the susceptible cells were treated either before or after infection, suggesting a possible prophylactic and therapeutic use. 5 CQ interferes with COVID-19's attempt to acidify the lysosomes & probably inhibits cathepsins, which needs a low pH for optimal cleavage of COVID-19 spike protein, a requirement for the formation of the autophagosome. 18 The Wuhan CoV (COVID-19) S-protein shares an almost identical 3-D structure in its RBD domain with SARS-CoV S-protein. Although relatively weaker than SARS-CoV, the Wuhan CoV S-protein has a strong binding affinity to human ACE2 receptors. Hence, the Wuhan CoV poses a significant risk for human transmission due to the S-protein-ACE2 binding pathway like SARS-CoV. 20 39 CQ has been found to function at both entry as well as post-entry stages of the COVID-19 infection in Vero E6 cells. The immune-modulating activity of CQ may also synergistically enhance its antiviral effect in vivo. After oral intake, CQ gets widely distributed in the whole body, including lung. The EC90 value of chloroquine against the COVID-19 in Vero E6 cells was 6.90μM, which is achievable clinically, as shown in the plasma of rheumatoid arthritis patients receiving 500 mg daily dose 7 . The low cost and good safety profile makes CQ a potentially clinically applicable drug against the COVID-19 infection. 7 The endemic malaria presence seems to protect certain populations from COVID-19 infection, especially in the least developed countries. The mechanism of action of some antimalarial drugs with antiviral property suggests their potential role in the chemoprophylaxis of the COVID-19 epidemic. 22