The major impact produced by the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) focused many researchers attention to find treatments that can suppress transmission or ameliorate the disease. Despite the very fast and large flow of scientific data on possible treatment solutions, none have yet demonstrated unequivocal clinical utility against coronavirus disease 2019 (COVID‑19). This work represents an exhaustive and critical review of all available data on potential treatments for COVID‑19, highlighting their mechanistic characteristics and the strategy development rationale. Drug repurposing, also known as drug repositioning, and target based methods are the most used strategies to advance therapeutic solutions into clinical practice. Current in silico, in vitro and in vivo evidence regarding proposed treatments are summarized providing strong support for future research efforts.
Repurposing was also a rapid response solution based on the experience with SARS-CoV, MERS-CoV, or with other viruses. Many of the repurposed drugs undergoing clinical trials were not tested in cell models against SARS-CoV-2, raising questions about their real efficacy. Even so, the cell models can be misleading because most compounds have not been tested on human cells and because only EC50 values are reported without clear information on the dose-response curve. Several conditions such as different multiplicities of infection or time of exposure can dramatically influence the EC50 values. There are several other concerns that are worth mentioning: the potential of a drug to reach the target tissue and how it would perform under complex, disease-altered conditions
Future research should focus on how the virus evades the immune response and try to better understand its interaction with the T and B cell responses, both in the humans and experimentally infected animals. The second goal should be to reveal and assess details of viral replication strategies and pathways, determining the relationship between sites of viral RNA replication and virus assembly, as well as the extent to which virus-host interactions are SARS-CoV-2 specific and organ-specific, using genomics and proteomics, as well as new reagents. A third future goal should be to translate new information about the structure and function of SARS-CoV-2 proteins into specific anti-virus therapies, particularly with respect to the SARS-CoV-2 proteins of unknown function. The next goal will be the understanding of viral pathogenesis, to design and develop effective live or attenuated safe vaccines. It is anticipated that, like other RNA viruses, subgenomic SARS-CoV-2 replicon systems adapted to lung, kidney, and even neuronal cell types will catalyse the understanding of SARS-CoV-2 biology.
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