Chloroquine as a potential inhibitor among all other
antivirals:
Chloroquine (CQ) is an acidotropic amine form of quinine. For decades CQ
is being used as a medication for the treatment and prevention of
malaria and for a variety of other viruses such as human
immuneodeficiency virus (HIV), Zika virus, Marburg virus, Dengue virus
and SARS-CoV-1 (Barnard et al., 2006). The reason behind this frequent
use is anti-inflammatory and immunomodulatory effects of this drug which
can be beneficial in treating COVID-19. The China National Centre for
Biotechnology Development found that CQ is Ⅰ of the Ⅲ drugs with
encouraging profile against SARS-Cov-2 caused by COVID-19 (Devaux,
Rolain, Colson, & Raoult, 2020). Chloroquine has multiple mechanisms of
action depending on the type of pathogen interaction. Chloroquine can
limit the pre-entry step of viral replication cycle by interfering with
viral particles binding to their intracellular receptors, it can also
inhibit pH dependent endosome mediated entry of enveloped viruses
(Barnard et al., 2006). This feature can be attributed in treating
COVID-19 as SARS-CoV-2 entry is also reported to be endosome mediated
(Wang et al., 2020). The pH intonation by CQ can diminish the proper
maturation of viral protein and recognition of viral antigens by
receptors. CQ can also inhibit post translational modifications of viral
proteins such as glycosylation which require low pH i.e. HIV and CQ
increase the pH (Vincent et al., 2005). During in-vitro studies CQ has
shown to deficit the glycosylation of angiotensin converting enzyme 2
(ACE2), a viral cell surface receptor (Wang et al., 2020). Chloroquine
works at both, entry and after entry stages of COVID-19 infection. Its
immune-modulating functions synergistically increase its antiviral
effects on animals as it is mostly distributed in the entire body as
well as lungs after oral administration. Recently CQ have been shown by
several studies to reduce SARS-CoV-2 viral load and duration of viremia
(Dong, Hu, & Gao, 2020). Till now, 15 clinical trials have been
conducted in China where each trial contained 100 patients to define the
safety and efficacy of CQ in treating COVID-19, however, their immune
modulatory effects also play a vital role in treating COVID-19 which
require further investigation (Zhang, Wang, Qi, Shen, & Li, 2020).
Suddenly, on May 25, 2020 WHO suspended the clinical trials of
chloroquine and hydroxyl-chloroquine as very potential treatment of
COVID-19 due to recent published study in Lancet by Mehra et al;
According to their findings, chloroquine and hydroxyl-chloroquine showed
serious side effects especially heart arrhythmia and many other
complications related cardiovascular diseases (Klopfenstein et al.,
2020).