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).