Repurposing of host-based therapeutic agents for the treatment of coronavirus disease 2019 (COVID-19): a link between antiviral and anticancer mechanisms?

ALONSO, DANIEL F.; FARINA, HERNÁN G.

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS

ELSEVIER SCIENCE BV

Año: 2020 vol. 56

0924-8579

Repurposing, also called repositioning or rediscovering, refers to the process ofdeveloping a known drug for a novel use, which is different from its original clinicalindication. This concept has focused greater attention on the search for viabletreatments in the context of the current pandemic. The article recently published bySerafin et al. in the International Journal of Antimicrobial Agents [1] presented aselection of repurposing drug candidates for potential use in the management ofcoronavirus disease 2019 (COVID-19). The authors conducted a systematic researchthrough PubMed, Scopus and Web of Science databases, and identified recent studiesinvestigating drugs from different pharmaceutical classes with antiviral activity againstSARS-CoV-2 and SARS-CoV. Remarkably, at least four drugs reported by Serafin et al.with promising early results in COVID-19 [1], including hydroxychloroquine,chloroquine, nitazoxanide and metformin, have also been previously explored asanticancer agents. The antimalarials hydroxychlroquine and chlroquine are known toinhibit autophagic pathways in aggressive metastatic cells, and potentiate the efficacyof chemotherapy in various types of cancers. Autophagy is considered a cytoprotectivemechanism that confers drug resistance, representing a key obstacle to effectivecancer treatment [2]. Likewise, the antiparasitic drug nitazoxanide induces cancer cellcytotoxicity under hypoxic conditions and it could be an excellent candidate to targetdormant cancer cells in hypoxic regions of tumors in combination with chemotherapyagents [3]. Metformin, an effective medication used in type 2 diabetes mellitus, is ableto modulate tumor cell signaling and metabolism. Although the underlyingmechanisms have not been completely characterized, metformin reduces tumor cellgrowth, inhibits the expression of microRNAs associated with tumorigenesis and limitsenergy availability by affecting mitochondrial metabolism [4]. Moreover, cell starvationcaused by metformin triggers the release of cytokines such as interleukins IL-6 and IL-8,and promotes recruitment of immune cells in tumor microenvironment [5]