Antimalarial artemisinin-based combination therapies (ACT) and COVID-19 in Africa: In vitro inhibition of SARS-CoV-2 replication by mefloquine-artesunate

Abstract

Objectives At the end of November 2019, a novel coronavirus responsible for respiratory tract infections (COVID-19) emerged in China. Despite drastic containment measures, this virus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread in Asia and Europe. The pandemic is ongoing with a particular hotspot in Southern Europe and America; many studies predicted a similar epidemic in Africa, as is currently seen in Europe and the United States of America. However, reported data have not confirmed these predictions. One of the hypotheses that could explain the later emergence and spread of COVID-19 pandemic in African countries is the use of antimalarial drugs to treat malaria, and specifically, artemisinin-based combination therapy (ACT). Methods The antiviral activity of fixed concentrations of ACT at concentrations consistent with those observed in human plasma when ACT is administered at oral doses for uncomplicated malaria treatment was evaluated in vitro against a clinically isolated SARS-CoV-2 strain (IHUMI-3) in Vero E6 cells. Results Mefloquine-artesunate exerted the highest antiviral activity with % inhibition of 72.1 ± 18.3 % at expected maximum blood concentration (C max ) for each ACT drug at doses commonly administered in malaria treatment. All the other combinations, artesunate-amodiaquine, artemether-lumefantrine, artesunate-pyronaridine, or dihydroartemisinin-piperaquine, showed antiviral inhibition in the same ranges (27.1 to 34.1 %). Conclusions Antimalarial drugs for which concentration data in the lungs are available are concentrated from 10 to 160 fold more in the lungs than in blood. These in vitro results reinforce the hypothesis that antimalarial drugs could be effective as an anti-COVID-19 treatment.

Antimalarial Drugs and COVID -19

“…However, some antimalarial drugs have been documented as future drugs for the treatment of COVID 19. Verifiable treatment with remodel antimalarial drugs such as chloroquine, hydroxychloroquine, azithromycin, pyronaridine and Artemisinin-based combination therapy (ACT) is going on [19].…”

“…In order to eliminate the evolution of resistance acquired by malaria parasites, the need to develop newer drug regimen [22]. A plant-based antimalarial drug was isolated from the Chinese plant Artemisia annua in seventies, World Health Organization recommended the use of artemisin in based combination therapy (ACT) as first line therapy for the treatment of uncomplicated malaria to increase the goal of treatment and prevent emergence of resistance to therapy [19,20,22]. Artemisinin derivatives have very short half-lives, thus using them as monotherapy requires doses over a period of 7 days.…”

“…In vitro activity of ACT against t SARS-CoV-2 sequel to oral administration of ACT for uncomplicated malaria treatment has been documented [19]. Also, artemisinin has shown anti-inflammatory effects as well as inhibition of interleukin-6 (IL-6) that serves critical function in the development of severe coronavirus disease 2019 (COVID-19) [25].…”

Re-reading ACT, BCG, and Low COVID-19 in Africa

“…Unlike chloroquine that was withdrawn in the late 1990s due to growing resistance to it by the plasmodium pathogen [9][10][11][12], most (n = 65/67, 97%) malaria endemic countries including 41 Africa countries adopted artemisinin combine terapy (ACT) as their first line of treatment for uncomplicated malaria in 2000 [13]. One study has demonstrated in vitro the clinical effectiveness of artemisinin in the treatment of COVID-19 [14].…”

Síndrome febril al regreso del trópico durante la pandemia de COVID-19

“…Desconocemos la influencia de SARS-CoV-2 en la evolución de la malaria grave, así como la posible influencia del tratamiento antipalúdico con derivado de la artemisinina que recibió el paciente. Gendrot et al 11 , tras comprobar actividad in vitro , proponen la utilidad de las combinaciones antimaláricas con alta concentración en parénquima pulmonar como terapias prospectivas en COVID-19 11 . Hipótesis que precisará de futuros estudios de investigación que aborden esta cuestión dada la ausente casuística comunicada de coinfección SARS-CoV-2 y Plasmodium falciparum en la literatura .…”