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

View ORCID ProfileKerry Gilmore, Yuyong Zhou, Santseharay Ramirez, Long V Pham, Ulrik Fahnoe, Shan Feng, Anna Offersgaard, Jakob Trimpert, Jens Bukh, Klaus Osterrieder, Judith Gottwein, Peter H Seeberger

doi: https://doi.org/10.1101/2020.10.05.326637 

PDF: https://www.biorxiv.org/content/10.1101/2020.10.05.326637v1.full.pdf

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.

Competing Interest Statement

K.G. is the director of ArtemiLife, Inc. K.G. and P.H.S. have a significant financial stake in ArtemiFlow GmbH, that is a shareholder in ArtemiLife, Inc.

https://www.biorxiv.org/content/10.1101/2020.10.05.326637v1

Airborne transmission of SARS-CoV-2

1. Kimberly A. Prather¹,
2. Linsey C. Marr²,
3. Robert T. Schooley³,
4. Melissa A. McDiarmid⁴,
5. Mary E. Wilson⁵,⁶,
6. Donald K. Milton⁷

1. DOI: 10.1126/science.abf0521 

1. PDF: https://science.sciencemag.org/content/early/2020/10/02/science.abf0521/tab-pdf

1. There is overwhelming evidence that inhalation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a major transmission route for coronavirus disease 2019 (COVID-19). There is an urgent need to harmonize discussions about modes of virus transmission across disciplines to ensure the most effective control strategies and provide clear and consistent guidance to the public. To do so, we must clarify the terminology to distinguish between aerosols and droplets using a size threshold of 100 μm, not the historical 5 μm (1). This size more effectively separates their aerodynamic behavior, ability to be inhaled, and efficacy of interventions.

   Viruses in droplets (larger than 100 μm) typically fall to the ground in seconds within 2 m of the source and can be sprayed like tiny cannonballs onto nearby individuals. Because of their limited travel range, physical distancing reduces exposure to these droplets. Viruses in aerosols (smaller than 100 μm) can remain suspended in air for many seconds to hours, like smoke, and be inhaled. They are highly concentrated near an infected person, so they can infect people most easily in close proximity. But aerosols containing infectious virus (2) can also travel more than 2 m and accumulate in poorly ventilated indoor air, leading to superspreading events (3).

   Individuals with COVID-19, many of whom have no symptoms, release thousands of virus-laden aerosols and far fewer droplets when breathing and talking (4–6). Thus, one is far more likely to inhale aerosols than be sprayed by a droplet (7), and so the balance of attention must be shifted to protecting against airborne transmission. In addition to existing mandates of mask-wearing, social distancing, and hygiene efforts, we urge public health officials to add clear guidance about the importance of moving activities outdoors, improving indoor air using ventilation and filtration, and improving protection for high-risk workers (8).

   https://science.sciencemag.org/content/early/2020/10/02/science.abf0521
   

How Moderna's Slowing COVID-19 Vaccine Enrollment Could Delay Interim Readout

Moderna Inc MRNA 4.56%'s CEO said last week that it will not seek emergency use authorization for its coronavirus vaccine candidate mRNA-1273 before the Nov. 3 U.S. presidential election.

Trial Enrollment Hits 94% Of Target:  Moderna's vaccine candidate is in a large-scale Phase 3 trial dubbed COVE with a target enrollment of 30,000 participants.

About 28,043, or 93.5%, of the targeted participants have been enrolled into the study, Moderna said in a late Friday tweet.

Of those people, 19,369 have been administered a second dose.

As of Friday, October 2, 2020, 28,043 participants have been enrolled in the Phase 3 COVE study and approximately 33% of participants enrolled cumulatively are from diverse communities. 19,369 participants have received their second vaccination.

— Moderna (@moderna_tx) October 2, 2020

The study protocol calls for administering two doses of mRNA-1273 — the first on day one and the second on day 29.

About 33% of the participants were from diverse communities, Moderna said. The company announced the dosing of the first patient in the trial on July 27.

Slowing Enrollment Behind The Delay? Moderna's muted expectations concerning an expedited rollout under an emergency use authorization is partly attributable to the slowdown in enrollment in recent weeks, according to one sell-side analyst. 

"Moderna's slower enrollment rate (partially due to an effort to include more diverse demographics) will likely push their earliest possible timeline for positive first interim efficacy readout until after the U.S. election," Raymond James analyst Steven Seedhouse said in a note.

The analyst said he expects Pfizer Inc. PFE 0.96%/BioNTech SE – ADR BNTX 9.5% to be first with an interim efficacy readout before the election and probably before the Oct. 22 general vaccine Adcom meeting.

Hard numbers substantiate the conjecture concerning the reason for the potential delay in Moderna's vaccine program. Source: Moderna

Nov. 25 is likely the date when enough safety data will become available to be included in an emergency use authorization application, Moderna CEO Stéphane Bancel told the Financial Times last week.

https://www.benzinga.com/analyst-ratings/analyst-color/20/10/17786180/how-modernas-slowing-covid-19-vaccine-enrollment-could-delay-interim-readout