salinomycin and Coronavirus-Infections

Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus, has catastrophic impacts on the global pig industry. Owing to the lack of effective vaccines and specific therapeutic options for PEDV, it is pertinent to develop new and available antivirals. This study identified, for the first time, a salinomycin that actively inhibited PEDV replication in Vero cells in a dose-dependent manner. Furthermore, salinomycin significantly inhibited PEDV infection by suppressing the entry and post-entry of PEDV in Vero cells. It did not directly interact with or inactivate PEDV particles, but it significantly ameliorated the activation of Erk1/2, JNK and p38MAPK signaling pathways that are associated with PEDV infection. This implied that salinomycin inhibits PEDV replication by altering MAPK pathway activation. Notably, the PEDV induced increase in reactive oxidative species (ROS) was not decreased, indicating that salinomycin suppresses PEDV replication through a pathway that is an independent pathway of viral-induced ROS. Therefore, salinomycin is a potential drug that can be used for treating PEDV infection.

Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Coronavirus Infections; MAP Kinase Signaling System; Porcine epidemic diarrhea virus; Pyrans; Reactive Oxygen Species; Signal Transduction; Swine; Swine Diseases; Vero Cells; Virus Replication

Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC

Topics: Animals; Anti-Inflammatory Agents; Antiviral Agents; Betacoronavirus; Cell Line; Chlorocebus aethiops; Coronavirus Infections; COVID-19; Drug Evaluation, Preclinical; Drug Repositioning; Humans; Niclosamide; Pandemics; Pneumonia, Viral; Pregnenediones; SARS-CoV-2; Vero Cells

Coronavirus disease outbreak caused a severe public health burden all over the world. Salinomycin (SAL) is a broad-spectrum antibiotic that had drawn attention in selective targeting of cancer and viral infections. Recent drug screen identified SAL as a potent antiviral agent against SARS-CoV-2. In this hypothesis, we discuss the potential of pulmonary delivery of SAL using nanostructured lipid carriers (NLCs) against SARS-CoV-2.

Topics: Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Carriers; Drug Repositioning; Endocytosis; Humans; Lipids; Lung; Nanostructures; Pandemics; Pneumonia, Viral; Pyrans; RNA, Viral; SARS-CoV-2

As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6.7 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus-specific vaccines, monoclonal antibodies and antiviral drugs against SARS-CoV-2 can be time-consuming and costly. Convalescent sera and safe-in-man broad-spectrum antivirals (BSAAs) are readily available treatment options. Here, we developed a neutralization assay using SARS-CoV-2 strain and Vero-E6 cells. We identified the most potent sera from recovered patients for the treatment of SARS-CoV-2-infected patients. We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. We found that a combination of orally available virus-directed nelfinavir and host-directed amodiaquine exhibited the highest synergy. Finally, we developed a website to disseminate the knowledge on available and emerging treatments of COVID-19.

Topics: Amodiaquine; Animals; Antiviral Agents; Betacoronavirus; Caco-2 Cells; Cell Line, Tumor; Chlorocebus aethiops; Coronavirus Infections; COVID-19; COVID-19 Serotherapy; Drug Therapy, Combination; Emetine; HEK293 Cells; Homoharringtonine; HT29 Cells; Humans; Immune Sera; Immunization, Passive; Indoles; Nelfinavir; Neutralization Tests; Pandemics; Pneumonia, Viral; Pyrans; Pyrroles; SARS-CoV-2; Vero Cells