Pyronaridine and artesunate are potential antiviral drugs against COVID-19 and influenza

Abstract

Since the first human case was reported in Wuhan Province, China in December 2019, SARS-CoV-2 has caused millions of human infections in more than 200 countries worldwide with an approximately 4.01% case-fatality rate (as of 27 July, 2020; based on a WHO situation report), and COVID-19 pandemic has paralyzed our global community. Even though a few candidate drugs, such as remdesivir (a broad antiviral prodrug) and hydroxychloroquine, have been investigated in human clinical trials, their therapeutic efficacy needs to be clarified further to be used to treat COVID-19 patients. Here we show that pyronaridine and artesunate, which are the chemical components of anti-malarial drug Pyramax®, exhibit antiviral activity against SARS-CoV-2 and influenza viruses. In human lung epithelial (Calu-3) cells, pyronaridine and artesunate were highly effective against SARS-CoV-2 while hydroxychloroquine did not show any effect at concentrations of less than 100 μM. In viral growth kinetics, both pyronaridine and artesunate inhibited the growth of SARS-CoV-2 and seasonal influenza A virus in Calu-3 cells. Taken together, we suggest that artesunate and pyronaridine might be effective drug candidates for use in human patients with COVID-19 and/or influenza, which may co-circulate during this coming winter season.

Artemisia annuaL. extracts inhibit thein vitroreplication of SARS-CoV-2 and two of its variants

“…A recent report showed that a number of artemisinin-related compounds have some anti-SARS-CoV-2 activity, with dihydroartemisinin, artesunate, and arteannuin B having IC 50 values <30 μM (Cao et al 2020), and dihydroartemisinin ACTs with 1-10 μM IC 50 s (Bae et al 2020). Artesunate was reported to have IC 50 values against SARS-CoV-2 of 7-12 μg/mL (0.7-1.2 μM; Gilmore et al 2020) and 2.6 μM (Bae et al 2020). Knowing that artemisinin is much more bioavailable per os when delivered via A. annua (Weathers et al 2011; Weathers et al 2014; Desrosiers et al 2020), we posited that encapsulated powdered dried leaves of A. annua may be a safe, cost-effective therapeutic to combat SARS-CoV-2 infections.…”

“…Artemisinin also blunts fibrosis (Larson et al 2019; Dolivo et al 2020), another problem experienced by SARS-CoV-2 survivors that causes more lasting damage to organs (Lechowicz et al 2020; Liu et al 2020a). A recent report showed that a number of artemisinin-related compounds have some anti-SARS-CoV-2 activity, with dihydroartemisinin, artesunate, and arteannuin B having IC 50 values <30 μM (Cao et al 2020), and dihydroartemisinin ACTs having 1-10 μM IC 50 values (Bae et al 2020). Artesunate was reported to have IC 50 values against SARS-CoV-2 of 7-12 μg/mL (0.7-1.2 μM; Gilmore et al 2020) and 2.6 μM (Bae et al 2020).…”

“…A recent report showed that a number of artemisinin-related compounds have some anti-SARS-CoV-2 activity, with dihydroartemisinin, artesunate, and arteannuin B having IC 50 values <30 μM (Cao et al 2020), and dihydroartemisinin ACTs having 1-10 μM IC 50 values (Bae et al 2020). Artesunate was reported to have IC 50 values against SARS-CoV-2 of 7-12 μg/mL (0.7-1.2 μM; Gilmore et al 2020) and 2.6 μM (Bae et al 2020).…”

Cationic Compounds with SARS-CoV-2 Antiviral Activity and Their Interaction with Organic Cation Transporter/Multidrug and Toxin Extruder Secretory Transporters

“…In the current study, we examined two sets of cationic compounds that have been recently proposed as potential COVID-19 therapeutics based on either in vitro activity against SARS-CoV-2 or published activity against other related viruses (Baker et al, 2020;Gawriljuk et al, 2020;Puhl et al, 2020;, as potential inhibitors of the primary transporters involved in the renal and hepatic secretion of organic cations, i.e., OCT1, OCT2, MATE1 and MATE2-K. The first set consisted of five antiparasitic/antimalarial compounds proposed to exhibit antiviral activity: chloroquine, hydroxychloroquine, and quinacrine (proposed to inhibit SARS-CoV-2 activity; (Uzunova et al, 2020;Pineda et al, 2021); and tilorone and pyronaridine (proposed to inhibit SARS-CoV-2 activity and investigated against activity of other viral infections, including Ebola, Chikungunya virus and other Coronavirus-caused diseases such as Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) MARV; (Bae et al, 2020;Ekins and Madrid, 2020;Lane and Ekins, 2020;Puhl et al, 2020). The second set of molecules consisted of the widely accessible, over the counter antiseptic molecules cetylpyridinium (frequently used in mouthwash) and miramistin (which is available in Russia), both of which display broad-spectrum antiviral activities that have garnered attention for their potential use in COVID-19 treatment (Mukherjee et al, 2017;Baker et al, 2020;Osmanov et al, 2020;Vergara-Buenaventura and Castro-Ruiz, 2020).…”

Indicator Regularized Non-Negative Matrix Factorization Method-Based Drug Repurposing for COVID-19

“…Artesunate-amodiaquine (AS-AQ), is also an antimalarial drug. Bae et al suggested that it is highly effective against COVID-19 infection that develops in human lung epithelial cells (52). Berberine, an isoquinoline alkaloid, inhibits DNA synthesis and reverse transcriptase activity.…”