homoharringtonine and Pneumonia--Viral

An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.

Topics: Adenosine Monophosphate; Alanine; Amides; Animals; Antimetabolites; Antiviral Agents; Betacoronavirus; Chlorocebus aethiops; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Emetine; Epithelial Cells; Homoharringtonine; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ribavirin; SARS-CoV-2; Vero Cells; Virus Replication

In December 2019, a new coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerged from China, causing pneumonia outbreaks first in the Wuhan region and then spread worldwide. Due to a lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the most efficient tool to find a therapeutic solution.. The aim of this study was to summarize in vitro data of current agents used for the management of SARS-CoV-2 all over the world.. A literature search of articles from January 2000 until April 2020 was performed using MEDLINE, EMBASE and the Cochrane Library to assess in vitro data of current or putative therapies for SARS-CoV-2.. Although in vitro studies are scarce, data regarding chloroquine, hydroxychloroquine, remdesivir, nitazoxanide, teicoplanin, ivermectin, lopinavir, homoharringtonine, and emetine seem promising.. Scientists all over the world should work together and increase their efforts in order to find feasible and efficient solutions against this new global viral threat.

Topics: Adenosine Monophosphate; Alanine; Betacoronavirus; China; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Repositioning; Emetine; Homoharringtonine; Humans; Hydroxychloroquine; Ivermectin; Lopinavir; Nitro Compounds; Pandemics; Pneumonia, Viral; SARS-CoV-2; Teicoplanin; Thiazoles

Topics: Adenosine Monophosphate; Alanine; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Emetine; Homoharringtonine; Humans; Lopinavir; Pandemics; Pneumonia, Viral; SARS-CoV-2; Severe acute respiratory syndrome-related coronavirus

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