tetano
Editor, Senior Moderator
Antiviral Res
. 2024 Mar 14:105859.
doi: 10.1016/j.antiviral.2024.105859. Online ahead of print. A combination of nirmatrelvir and ombitasvir boosts inhibition of SARS-CoV-2 replication
Christopher Moon[SUP] 1 [/SUP], Eleanor Porges[SUP] 2 [/SUP], Adam Roberts[SUP] 2 [/SUP], Joanna Bacon[SUP] 2 [/SUP]
Affiliations
Antiviral therapeutics are highly effective countermeasures for the treatment of coronavirus disease 2019 (COVID-19). However, development of resistance to antivirals undermines their effectiveness. Combining multiple antivirals during patient treatment has the potential to overcome the evolutionary selective pressure towards antiviral resistance, as well as provide a more robust and efficacious treatment option. The current evidence for effective antiviral combinations to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication is limited. Here, we demonstrate a combination of nirmatrelvir with ombitasvir, to jointly bring about potent inhibition of SARS-CoV-2 replication. We developed an in vitro 384- well plate cytopathic effect assay for the evaluation of antiviral combinations against Calu-3 cells infected with SARS-CoV-2 and found, that a combination of ombitasvir and nirmatrelvir was synergistic; thereby decreasing the nirmatrelvir IC[SUB]50[/SUB] by approx. 16-fold. The increased potency of the nirmatrelvir-ombitasvir combination, over nirmatrelvir alone afforded a greater than 3 log[SUB]10[/SUB] reduction in viral titre, which is sufficient to fully prevent the detection of progeny SARS-CoV-2 viral particles at 48 h post infection. The mechanism of this potentiated effect was shown to be, in-part, due to joint inhibition of the 3-chymotrypsin-like protease via a positive allosteric modulation mechanism.
Keywords: Antiviral combinations; COVID-19; Nirmatrelvir; Ombitasvir; Potentiation; SARS-CoV-2.
. 2024 Mar 14:105859.
doi: 10.1016/j.antiviral.2024.105859. Online ahead of print. A combination of nirmatrelvir and ombitasvir boosts inhibition of SARS-CoV-2 replication
Christopher Moon[SUP] 1 [/SUP], Eleanor Porges[SUP] 2 [/SUP], Adam Roberts[SUP] 2 [/SUP], Joanna Bacon[SUP] 2 [/SUP]
Affiliations
- PMID: 38492891
- DOI: 10.1016/j.antiviral.2024.105859
Antiviral therapeutics are highly effective countermeasures for the treatment of coronavirus disease 2019 (COVID-19). However, development of resistance to antivirals undermines their effectiveness. Combining multiple antivirals during patient treatment has the potential to overcome the evolutionary selective pressure towards antiviral resistance, as well as provide a more robust and efficacious treatment option. The current evidence for effective antiviral combinations to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication is limited. Here, we demonstrate a combination of nirmatrelvir with ombitasvir, to jointly bring about potent inhibition of SARS-CoV-2 replication. We developed an in vitro 384- well plate cytopathic effect assay for the evaluation of antiviral combinations against Calu-3 cells infected with SARS-CoV-2 and found, that a combination of ombitasvir and nirmatrelvir was synergistic; thereby decreasing the nirmatrelvir IC[SUB]50[/SUB] by approx. 16-fold. The increased potency of the nirmatrelvir-ombitasvir combination, over nirmatrelvir alone afforded a greater than 3 log[SUB]10[/SUB] reduction in viral titre, which is sufficient to fully prevent the detection of progeny SARS-CoV-2 viral particles at 48 h post infection. The mechanism of this potentiated effect was shown to be, in-part, due to joint inhibition of the 3-chymotrypsin-like protease via a positive allosteric modulation mechanism.
Keywords: Antiviral combinations; COVID-19; Nirmatrelvir; Ombitasvir; Potentiation; SARS-CoV-2.