COVID-19 is an emerging outbreak similar to previous pandemics caused by Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Till date, SARS-CoV-2 infection is still spreading, representing a major threat to public health, where several control measures are being practiced in order to culminate its spread. The research and development of new drugs require a lot of funding in addition to being a slow and costly process. As a result, new techniques have been proposed to streamline this process. The repositioning or repurposing of drugs represents an attractive strategy, presenting a promising way to introduce new drugs. Currently, numerous reused drugs are already available in the market and are in practice. In this review, it was observed that the antiviral drugs Entricitabine and Tenofovir display potential therapeutic efficacy in preclinical studies. Therefore, in silico analyses were considered a potential tool for predicting the effectiveness of drugs, mainly as an effective approach to encourage a complementary in vitro and in vivo antiviral evaluation.