Asenapine for COVID-19

 Asenapine has been reported as potentially beneficial for COVID-19 in the following studies.
COVID-19 involves the interplay of 350+ viral and host proteins and factors providing many therapeutic targets. Scientists have proposed 10,000+ potential treatments. c19early.org analyzes 210+ treatments. We have not reviewed asenapine in detail.
Loucera et al., Drug repurposing for COVID-19 using machine learning and mechanistic models of signal transduction circuits related to SARS-CoV-2 infection, Signal Transduction and Targeted Therapy, doi:10.1038/s41392-020-00417-y
Xiong et al., Several FDA-approved drugs effectively inhibit SARS-CoV-2 infection in vitro, bioRxiv, doi:10.1101/2020.06.05.135996
AbstractTo identify drugs that are potentially used for the treatment of COVID-19, the potency of 1403 FDA-approved drugs were evaluated using a robust pseudovirus assay and the candidates were further confirmed by authentic SARS-CoV-2 assay. Four compounds, Clomiphene (citrate), Vortioxetine, Vortioxetine (hydrobromide) and Asenapine (hydrochloride), showed potent inhibitory effects in both pseudovirus and authentic virus assay. The combination of Clomiphene (citrate), Vortioxetine and Asenapine (hydrochloride) is much more potent than used alone, with IC50 of 0.34 μM.
Yuan et al., Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system, Pharmacological Research, doi:10.1016/j.phrs.2020.104960
Ku et al., Repurposing Screens of FDA-Approved Drugs Identify 29 Inhibitors of SARS-CoV-2, Journal of Microbiology and Biotechnology, doi:10.4014/jmb.2009.09009
Bakowski et al., Drug repurposing screens identify chemical entities for the development of COVID-19 interventions, Nature Communications, doi:10.1038/s41467-021-23328-0
AbstractThe ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. Here, we describe a screening pipeline for the discovery of efficacious SARS-CoV-2 inhibitors. We screen a best-in-class drug repurposing library, ReFRAME, against two high-throughput, high-content imaging infection assays: one using HeLa cells expressing SARS-CoV-2 receptor ACE2 and the other using lung epithelial Calu-3 cells. From nearly 12,000 compounds, we identify 49 (in HeLa-ACE2) and 41 (in Calu-3) compounds capable of selectively inhibiting SARS-CoV-2 replication. Notably, most screen hits are cell-line specific, likely due to different virus entry mechanisms or host cell-specific sensitivities to modulators. Among these promising hits, the antivirals nelfinavir and the parent of prodrug MK-4482 possess desirable in vitro activity, pharmacokinetic and human safety profiles, and both reduce SARS-CoV-2 replication in an orthogonal human differentiated primary cell model. Furthermore, MK-4482 effectively blocks SARS-CoV-2 infection in a hamster model. Overall, we identify direct-acting antivirals as the most promising compounds for drug repurposing, additional compounds that may have value in combination therapies, and tool compounds for identification of viral host cell targets.