Remdesivir–ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2

Abstract

A key element for the prevention and management of COVID-19 is the development of effective therapeutics. Drug combination strategies of repurposed drugs offer several advantages over monotherapies, including the potential to achieve greater efficacy, the potential to increase the therapeutic index of drugs and the potential to reduce the emergence of drug resistance. Here, we report on the in vitro synergistic interaction between two FDA approved drugs, remdesivir and ivermectin resulting in enhanced antiviral activity against SARS-CoV-2. Whilst the in vitro synergistic activity reported here does not support the clinical application of this combination treatment strategy, due to insufficient exposure of ivermectin in vivo , the data do warrant further investigation. Efforts to define the mechanisms underpinning the observed synergistic action, could lead to the development of novel therapeutic treatment strategies.

D,L-Lysine-Acetylsalicylate + Glycine (LASAG) Reduces SARS-CoV-2 Replication and Shows an Additive Effect with Remdesivir

“…Combination therapies are standard for the treatment of viral infections due to a better efficacy, decreased toxicity and the prevention of resistance emergence compared to single antivirals [45]. With the help of the webtool Syngeryfinder 2.0, several pharmacological studies were carried out to find useful drug combinations that could be repurposed to treat COVID-19 [62][63][64]. Our data clearly indicate an additive effect on SARS-CoV-2 inhibition by combining LASAG with remdesivir in vitro.…”

Interaction of the new inhibitor paxlovid (PF-07321332) and ivermectin with the monomer of the main protease SARS-CoV-2: A volumetric study based on molecular dynamics, elastic networks, classical thermodynamics and SPT

“…All MD simulations and additional adjustments were performed using cosgene/myPresto. Cosgene/myPresto which is available at https://www.mypresto5.jp/en/ ( Aggarwal and Biswas, 2020 , Alvarado et al, 2015 , Jeffreys et al, 2022 , Jiang et al, 2014 ).…”

Small molecules in the treatment of COVID-19

“…3 ). 23 , 24 Mutagens incorporated into RNA strands can cause permanent mutations. 25 , 26 Obligate terminators lacking a 3-OH group will terminate RNA extensions immediately, while non-obligate chain termination usually proceeds when a drug contains both a natural base and a 3-OH on the sugar but has a modified ribose skeleton that disrupts translocation.…”