Epirubicin for COVID-19

The SARS-CoV-2 pandemic has posed a tremendous burden globally, highlighting the urgent need for new effective antivirals that are possibly useful against future emerging Coronaviruses (hCoVs). In this context, major efforts were focused on the inhibition of highly conserved and essential targets playing a pivotal role in viral replication. Among them, SARS-CoV-2 nsp13 stands out, being the most conserved enzyme within hCoVs. Following our previous reports describing the identification of indole-based diketo acid (DKA) derivatives as SARS-CoV-2 nsp13 inhibitors endowed with antiviral activity, we applied a scaffold hopping strategy to identify new nsp13 inhibitors. Therefore, we investigated a series of 4-phenyl pyrrolyl DKAs and their structural analogs characterized by molecular simplification or DKA isosteric replacement. The derivatives showed potency against both nsp13-associated activities exhibiting measurable IC50s in the low micromolar/submicromolar range, highlighting a promising dual inhibitory profile accordingly. Structure–activity relationship (SAR) studies were performed, highlighting the main structural features increasing the activity of the different compound classes. Interestingly, SAR trends were confirmed in the presence of the BSA/TCEP system despite variations in potency. To shed light on the interaction of the best acting compounds 13b, 15a, and 17d, docking studies were performed, suggesting a putative binding mode in agreement with our previous findings.

AbstractSince the emergence of SARS‐CoV‐2 at the end of 2019, the virus has caused significant global health and economic disruptions. Despite the rapid development of antiviral vaccines and some approved treatments such as remdesivir and paxlovid, effective antiviral pharmacological treatments for COVID‐19 patients remain limited. This study explores Nsp15, a 3′‐uridylate‐specific RNA endonuclease, which has a critical role in immune system evasion and hence in escaping the innate immune sensors. We conducted a comprehensive drug repurposing screen and identified 44 compounds that showed more than 55% inhibition of Nsp15 activity in a real‐time fluorescence assay. A validation pipeline was employed to exclude unspecific interactions, and dose–response assays confirmed 29 compounds with an IC50 below 10 μM. Structural studies, including molecular docking and x‐ray crystallography, revealed key interactions of identified inhibitors, such as TAS‐103 and YM‐155, with the Nsp15 active site and other critical regions. Our findings show that the identified compounds, particularly those retaining potency under different assay conditions, could serve as promising hits for developing Nsp15 inhibitors. Additionally, the study emphasizes the potential of combination therapies targeting multiple viral processes to enhance treatment efficacy and reduce the risk of drug resistance. This research contributes to the ongoing efforts to develop effective antiviral therapies for SARS‐CoV‐2 and possibly other coronaviruses.

The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.

The present coronavirus disease 2019 (COVID-19) pandemic scenario has posed a difficulty for cancer treatment. Even under ideal conditions, malignancies like small cell lung cancer (SCLC) are challenging to treat because of their fast development and early metastases. The treatment of these patients must not be jeopardized, and they must be protected as much as possible from the continuous spread of the COVID-19 infection. Initially identified in December 2019 in Wuhan, China, the contagious coronavirus illness 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Finding inhibitors against the druggable targets of SARS-CoV-2 has been a significant focus of research efforts across the globe. The primary motivation for using molecular modeling tools against SARS-CoV-2 was to identify candidates for use as therapeutic targets from a pharmacological database. In the published study, scientists used a combination of medication repurposing and virtual drug screening methodologies to target many structures of SARS-CoV-2. This virus plays an essential part in the maturation and replication of other viruses. In addition, the total binding free energy and molecular dynamics (MD) modeling findings showed that the dynamics of various medications and substances were stable; some of them have been tested experimentally against SARS-CoV-2. Different virtual screening (VS) methods have been discussed as potential means by which the evaluated medications that show strong binding to the active site might be repurposed for use against SARS-CoV-2.