5.3.2 Chloroquine, hydroxychloroquine and azithromycin
Chloroquine, as a drug extensively utilized in anti-malaria and
autoimmune diseases, has been found to be a potential broad-spectrum
antiviral agent (Savarino et al., 2006). It can prevent viral infections
via elevating the endosomal pH needed for virus-cell fusion and
disturbing the glycosylation of SARS-CoV cell receptors (Figure 7)
(Vincent et al., 2005). Gao et al. revealed that chloroquine phosphate
was effective in the therapy of COVID-19-associated pneumonia (Gao et
al., 2020). Wang and coworkers also conducted in vitro study, and
they found that it is an ideal candidate antiviral drug against
SARS-CoV-2 infection in Vero E6 cells with EC50 value of around one μM
(Wang et al., 2020b). Although several trials had verified that
chloroquine suppresses the exacerbation of COVID-19, the optimal dosage
of chloroquine will require to be evaluated in future trials (Gao et
al., 2020).
Hydroxychloroquine is an analog of chloroquine, and there are few
studies on its interaction (Jallouli et al., 2015). In previous SARS
outbreaks, hydroxychloroquine was found to possess anti-SARS-CoV
capacity in vitro (Figure 7) (Biot et al., 2006). In line with
the research of Yao et al., by applying a physiologically based
pharmacokinetic model, they found that hydroxychloroquine is more
effective than chloroquine in Vero cells infected with SARS-CoV-2 (Yao
et al., 2020). Of note, it has been revealed that cytokines IL-6 and
IL-10 are elevated in response to SARS-CoV-2 infection, which may induce
the cytokine storm (Figure 5), which in turn cause multiple organ
failure and death (Huang et al., 2020). Both chloroquine and
hydroxychloroquine possess immunomodulatory effects and can inhibit such
immune responses (Schrezenmeier and Dörner, 2020). Hence, Chinese
hospitals and Oxford University had initiated 21 clinical studies to
evaluate the efficacy of these drugs in COVID-19 infection. The further
crucial study may relate with the determination of whether the benefit
of chloroquine treatment is hinged on the age of the patients as well as
the clinical manifestations (Touret and de Lamballerie, 2020).
According to reports, azithromycin is can suppress Zika virus and Ebola
virus in vitro and can be harnessed to restrain severe
respiratory infections in infected patients. Gautret and colleagues
found that azithromycin can significantly reinforce the efficacy of
hydroxychloroquine after treating 20 patients with severe COVID-19
(Gautret et al., 2020). In this regard, the regimen of
hydroxychloroquine, in combination with azithromycin may be a potential
alternative to remdesivir in the therapy of COVID-19 diseases in the
future.