In vitro efficacy of Artemisinin-based treatments against SARS-CoV-2

Abstract

Effective and affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are needed. We report in vitro efficacy of Artemisia annua extracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. The latter two are approved active pharmaceutical ingredients of anti-malarial drugs.Proof-of-concept for prophylactic efficacy of the extracts was obtained using a plaque-reduction assay in VeroE6 cells. Subsequent concentration-response studies using a high-throughput antiviral assay, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that pretreatment and treatment with extracts, artemisinin, and artesunate inhibited SARS-CoV-2 infection of VeroE6 cells. In treatment assays, artesunate (50% effective concentration (EC50): 7 μg/mL) was more potent than the tested plant extracts (128-260 μg/mL) or artemisinin (151 μg/mL) and artemether (>179 μg/mL), while generally EC50 in pretreatment assays were slightly higher. The selectivity index (SI), calculated based on treatment and cell viability assays, was highest for artemisinin (54), and roughly equal for the extracts (5-10), artesunate (6) and artemether (<7). Similar results were obtained in human hepatoma Huh7.5 cells. Peak plasma concentrations of artesunate exceeding EC50 values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.

Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 in Vitro

“…Sigmoidal concentration response curves were fitted and EC50 values calculated as described previously using Graphpad Prism 8.0.0 with a bottom constraint of 0 applying the formula Y= Top/(1+10 (Log10EC50-X)*HillSlope ). 31,85 Representative images from concentration-response antiviral treatment assays are shown by Gilmore, Zhou et al 86…”

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.…”

In vitro efficacy of Artemisia extracts against SARS-CoV-2

“…Among the active samples were extracts of A. annua and A. afra plants (Figure 3). This finding was surprising considering that A. afra does not contain artemisinin and even more so since synthetic artesunate, a pharmacokinetically improved derivative of artemisinin, proved most active in previous in vitro SARS-CoV-2 inhibition studies [16,25]. Our findings suggest that not just artemisinin but also other compounds present in the Artemisia extracts have inhibitory effects towards SARS-CoV-2.…”

“…In addition to pure, semi-synthetic substances, Artemisia teas and plant material have been explored for use to treat different diseases. [14] A. annua extract had shown anti-viral activity in vitro against SARS-CoV in 2005 [15] and SARS-CoV-2 (EC50 value: 2.5 µg/mL) [16] [18]. Standardized A. annua extracts with high artemisinin content are currently being studied in an ongoing phase 2 clinical trial against COVID- 19 [17].…”

“…Standardized A. annua extracts with high artemisinin content are currently being studied in an ongoing phase 2 clinical trial against COVID- 19 [17]. Artesunate 2 was significantly more active than A. annua extracts against SARS-CoV-2 in vitro [16]. The excellent safety profiles of artemisinin-based drugs in humans and their ready availability for worldwide distribution at a relatively low cost render them attractive repurposing candidates for treatment of COVID-19.…”