In Vitro Efficacy of Antiviral Agents against Omicron Subvariant BA.4.6

Takashita, Emi; Yamayoshi, Seiya; Halfmann, Peter; Wilson, Nancy A.; Ries, Hunter; Richardson, Alex; Bobholz, Max; Vuyk, William; Maddox, Robert James; Baker, David; Friedrich, Thomas C.; O’Connor, David H.; Uraki, Ryuta; Ito, Mutsumi; Sakai‐Tagawa, Yuko; Adachi, Eisuke; Saito, Makoto; Koga, Michiko; Tsutsumi, Takeshi; Iwatsuki‐Horimoto, Kiyoko; Kiso, Maki; Yotsuyanagi, Hiroshi; Watanabe, Shinji; Hasegawa, Hideki; Imai, Masaki; Kawaoka, Yoshihiro

doi:10.1056/nejmc2211845

Cited by 31 publications

(21 citation statements)

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“…Since then CoV2 has continued to evolve, there now being additional Omicron variants (BA.4, BA.5, BA.2.12.1, BA.2.75, XBB) and "Scrabble" subvariants (BQ.1 and BQ1.1) with Spike protein sequences that further desensitize the virus to in vitro neutralization by many (but not all) monoclonal therapies (109)(110)(111)(112), as well as convalescent plasma (113). Since Omicron has a higher tropism for the nasopharyngeal and oral cavities than that of pre-Omicron lineages (39)(40)(41)(42)(43), saliva antibodies may be more important inhibitors of Omicron transmission than plasma or lower airway antibodies, and saliva-the collection of which is far easier than blood-may be more suitable for rapid determination of whether someone has neutralizing capacity against future CoV2 variants that have yet to emerge.…”

Section: Discussionmentioning

confidence: 99%

The emergence of SARS-CoV-2 lineages and associated antibody responses among asymptomatic individuals in a large university community

Merling

Williams

Mahfooz

et al. 2023

Preprint

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SARS-CoV-2 (CoV2) infected, asymptomatic individuals are an important contributor to COVID transmission. CoV2-specific immunoglobulin (Ig), as generated by the immune system following infection or vaccination, has helped limit CoV2 transmission from asymptomatic individuals to susceptible populations (e.g. elderly). Here, we describe the relationships between COVID incidence and CoV2 lineage, viral load, saliva Ig levels (CoV2-specific IgM, IgA and IgG) and inhibitory capacity in asymptomatic individuals between Jan 2021 and May 2022. These data were generated as part of a large university COVID monitoring program and demonstrate that COVID incidence among asymptomatic individuals occurred in waves which mirrored those in surrounding regions, with saliva CoV2 viral loads becoming progressively higher in our community until vaccine mandates were established. Among the unvaccinated, infection with each CoV2 lineage (pre-Omicron) resulted in saliva Spike-specific IgM, IgA and IgG responses, the latter increasing significantly post-infection and being more pronounced than N-specific IgG responses. Vaccination resulted in significantly higher Spike-specific IgG levels compared to unvaccinated infected individuals, and uninfected vaccinees saliva was more capable of inhibiting Spike function. Vaccinees with breakthrough Delta infections had Spike-specific IgG levels comparable to those of uninfected vaccinees; however, their ability to inhibit Spike binding was diminished. These data demonstrate that COVID vaccines achieved hoped-for effects in our community, including the generation of mucosal antibodies that inhibit Spike and lower community viral loads, and suggest breakthrough Delta infections were not due to an absence of vaccine-elicited Ig, but instead limited Spike binding activity in the face of high community viral loads.

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Section: Discussionmentioning

confidence: 99%

The emergence of SARS-CoV-2 lineages and associated antibody responses among asymptomatic individuals in a large university community

Merling

Williams

Mahfooz

et al. 2023

Preprint

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“…When looking specifically at Omicron sublineages, remdesivir retained its activity across all major circulating sublineages, i.e., BA.1, BA.2, BA.4 and BA.5 (Veklury, 2022), as well as, most recently, BQ.1.1 and XBB (Imai et al, 2022). The same is true for molnupiravir, which has retained its antiviral efficacy against BA.1 ( Uraki et al, 2022b) and BA.2 in vitro (Takashita et al, 2022a) and in hamster models (Uraki et al, 2022a), and in vitro against BA.5 (Takashita et al, 2022b), BQ.1.1 and XBB (Imai et al, 2022).…”

Section: Antiviral Activity Of Rdrp Inhibitors Across Sars-cov-2 Vari...mentioning

confidence: 97%

“…From the data available so far, nirmatrelvir has retained antiviral activity across the most important dominant variants: Alpha, Delta (Vangeel et al, 2022), Omicron BA.1 (Joyce et al, 2022;Vangeel et al, 2022), BA.2 (Takashita et al, 2022a;Uraki et al, 2022a), BA.5 (Takashita et al, 2022b), BQ.1.1 and XBB (Imai et al, 2022).…”

Section: Protease Inhibitor-nirmatrelvir/ Ritonavirmentioning

confidence: 99%

Therapeutic developments for SARS-CoV-2 infection—Molecular mechanisms of action of antivirals and strategies for mitigating resistance in emerging variants in clinical practice

et al. 2023

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This article systematically presents the current clinically significant therapeutic developments for the treatment of COVID-19 by providing an in-depth review of molecular mechanisms of action for SARS-CoV-2 antivirals and critically analyzing the potential targets that may allow the selection of resistant viral variants. Two main categories of agents can display antiviral activity: direct-acting antivirals, which act by inhibiting viral enzymes, and host-directed antivirals, which target host cell factors that are involved in steps of the viral life cycle. We discuss both these types of antivirals, highlighting the agents that have already been approved for treatment of COVID-19, and providing an overview of the main molecules that are currently in drug development. Direct-acting antivirals target viral enzymes that are essential in the viral life cycle. Three direct-acting antivirals are currently in use: two are nucleoside analogs that inhibit the RNA-dependent RNA polymerase of SARS-CoV-2, i.e., remdesivir and molnupiravir, and the third one, nirmatrelvir/ritonavir, is an inhibitor of SARS-CoV-2 main protease. The potential for induction of viral resistance is discussed for each of these antivirals, along with their clinical activity on each of the SARS-CoV-2 variants and sublineages that have been dominant over the course of the pandemic, i.e., Alpha, Delta, as well as Omicron and its sublineages BA.1, BA.2, BA.5, BQ.1 and XBB. Host-directed antivirals are currently in preclinical or clinical development; these agents target host cell enzymes that are involved in facilitating viral entry, replication, or virion release. By blocking these enzymes, viral replication can theoretically be effectively stopped. As no SARS-CoV-2 host-directed antiviral has been approved so far, further research is still needed and we present the host-directed antivirals that are currently in the pipeline. Another specific type of agents that have been used in the treatment of COVID-19 are neutralizing antibodies (NAbs). Their main binding site is the spike protein, and therefore their neutralization activity is influenced by mutations occurring in this region. We discuss the main changes in neutralization activity of NAbs for the most important dominant SARS-CoV-2 variants. Close monitoring of emerging variants and sublineages is still warranted, to better understand the impact of viral mutations on the clinical efficiency of antivirals and neutralizing antibodies developed for the treatment of COVID-19.

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“…Los datos recientes del Instituto Nacional de Enfermedades Infecciosas de Tokio, Japón, sugieren que remdesivir, molnupiravir y nirmatrelvir y los anticuerpos monoclonales bebtelovimab e imdevimab conservan su eficacia contra la BA.4.6 in vitro. Los resultados también indican que los anticuerpos monoclonales casirivimab, sotrovimab, tixagevimab y cilgavimab pueden no ser eficaces contra la BA.4.6 (18) . Sin embargo, en el caso de BQ.1.1 y las 6+ mutaciones hay evidencia preocupante de escape inmunológico, por la pérdida anticipada de eficacia de los anticuerpos monoclonales evusheld o bebtlelovimab.…”

Section: Infección Por Las Nuevas Subvariantes Sars-cov-2 Con El Uso ...unclassified

El enigma del coronavirus – Reinfecciones por COVID-19, COVID prolongado – Vacunas bivalentes - La gestante – Derechos humanos y Ética

Romero

2022

Rev peru ginecol obstet.

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In Vitro Efficacy of Antiviral Agents against Omicron Subvariant BA.4.6

Cited by 31 publications

References 1 publication

The emergence of SARS-CoV-2 lineages and associated antibody responses among asymptomatic individuals in a large university community

The emergence of SARS-CoV-2 lineages and associated antibody responses among asymptomatic individuals in a large university community

Therapeutic developments for SARS-CoV-2 infection—Molecular mechanisms of action of antivirals and strategies for mitigating resistance in emerging variants in clinical practice

El enigma del coronavirus – Reinfecciones por COVID-19, COVID prolongado – Vacunas bivalentes - La gestante – Derechos humanos y Ética

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