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Elitsa Gotseva*, Elena Filipova, Katya Uzunova, Velichka Pavlova, Silvia Hristova and Toni Vekov
COVID-19 caused global pandemic with no specific treatment available so far. Developing new drugs usually requires time and is impractical to meet the immediate global challenge. Repurposing of drugs is a good alternative because these medicines have well established safety and efficacy profile. It is likely to not achieve a significant clinical benefit as a result of using a single drug but a careful well studied combination may lead to a better efficacy. This article emphasizes the potential combination of 3 well known drugs already used as single agents against COVID-19 with contradictory results – Hydroxychloroquine, Ivermectin and Colchicine. We try to give a closer look of their mechanism of action and the possibility to be effective at different stages of the treatment when used in one regimen. Hydroxychloroquine inhibits glycosylation of ACE2 receptors and thereby prevents COVID-19 from binding to the receptor and entering into host cells. It also prevents from conversion of early endosome into late endosome through increase of the pH. Ivermectin inhibits the nuclear transport through IMP α/β1 and prevents the virus RNA from entering into the nucleus. Colchicine with its anti-inflammatory and anti-viral properties may have a potential benefit in severe COVID-19 related to an inhibitory effect on the activation, destabilization, and degradation of inflammasomes. Further investigations followed by well-designed clinical studies of these drugs are recommended before this theory be rejected or confirmed.