Efficacy of Antibodies and Antiviral Drugs against Covid-19 Omicron Variant

Takashita, Emi; Iwamoto, Noriko; Yamayoshi, Seiya; Sakai‐Tagawa, Yuko; Fujisaki, Seiichiro; Ito, Mutsumi; Iwatsuki‐Horimoto, Kiyoko; Chiba, Shiho; Halfmann, Peter; Nagai, Hirokazu; Saito, Makoto; Adachi, Eisuke; Sullivan, David J.; Pekosz, Andrew; Watanabe, Shinji; Maeda, Kenji; Imai, Masaki; Yotsuyanagi, Hiroshi; Mitsuya, Hiroaki; Ohmagari, Norio; Takeda, Makoto; Hasegawa, Hideki; Kawaoka, Yoshihiro

doi:10.1056/nejmc2119407

Cited by 369 publications

(391 citation statements)

References 4 publications

Supporting

Mentioning

342

Contrasting

Unclassified

Order By: Relevance

“…We tested REGN10987/REGN10933, S309 (the precursor of sotrovimab), and COV2-2196/COV2-2130 for their therapeutic e cacy against BA.2. We synthesized these mAbs according to publicly available sequences without modi cations in their Fc regions, as described previously 14,37 . Syrian hamsters were inoculated with 10 3 PFU of CoV-2/UT-HP095-1N/Human/2020/Tokyo (D614G; HP095) or BA.2 (NCD1288), and one day later were injected intraperitoneally with S309 (5 mg/kg), the REGN10987/REGN10933 combination (2.5 mg/kg each), or the COV2-2196/COV2-2130 combination (2.5 mg/kg each) (Fig.…”

Section: Ba2 and Ba1 Omicron Variants Show Similar Replication And Pa...mentioning

confidence: 99%

“…Recently, we and others showed that BA.1 variants are less pathogenic in animal models than previously circulating variants of concern (VOC) [6][7][8] , consistent with preliminary clinical data in humans 9 . Moreover, other studies have reported that BA.1 variants show reduced sensitivity to vaccine-or infection-induced antibodies, as well as some therapeutic monoclonal antibodies (mAbs) [10][11][12][13][14] . The spike (S) protein of SARS-CoV-2 mediates viral receptor-binding and membrane fusion, both of which are essential for viral infection of host cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization and antiviral susceptibility of SARS-CoV-2 Omicron/BA.2

Kawaoka

Uraki

Kiso

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

The recent emergence of SARS-CoV-2 Omicron variants possessing large numbers of mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies, and antiviral drugs for COVID-19 against these variants1,2. While the original Omicron lineage, BA.1, has become dominant in many countries, BA.2 has been detected in at least 67 countries and has become dominant in the Philippines, India, and Denmark. Here, we evaluated the replicative ability and pathogenicity of an authentic infectious BA.2 isolate in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone3, we observed similar infectivity and pathogenicity in mice and hamsters between BA.2 and BA.1, and less pathogenicity compared to early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from COVID-19 convalescent individuals and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987/REGN10933, COV2-2196/COV2-2130, and S309) and antiviral drugs (molnupiravir, nirmatrelvir, and S-217622) can restrict viral infection in the respiratory organs of hamsters infected with BA.2. These findings suggest that the replication and pathogenicity of BA.2 is comparable to that of BA.1 in rodents and that several therapeutic monoclonal antibodies and antiviral compounds are effective against Omicron/BA.2 variants.

show abstract

Section: Ba2 and Ba1 Omicron Variants Show Similar Replication And Pa...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization and antiviral susceptibility of SARS-CoV-2 Omicron/BA.2

Kawaoka

Uraki

Kiso

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Notably, BA.2 has initiated outcompeting BA.1 3 , suggesting that BA.2 is more transmissible than BA. 1. In a few months since the emergence of BA.1, we and others revealed the virological characteristics of BA.1 [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . For instance, BA.1 is highly resistant to the vaccine-induced humoral immunity and antiviral drugs [4][5][6][7][8][9][10][11][16][17][18][19] .…”

Section: Introductionmentioning

confidence: 99%

“…1. In a few months since the emergence of BA.1, we and others revealed the virological characteristics of BA.1 [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . For instance, BA.1 is highly resistant to the vaccine-induced humoral immunity and antiviral drugs [4][5][6][7][8][9][10][11][16][17][18][19] . Also, the spike (S) protein of BA.1 is less efficiently cleaved by furin and less fusogenic than those of Delta and an ancestral SARS-CoV-2 belonging to the B.1.1 lineage 11,12 .…”

Section: Introductionmentioning

confidence: 99%

Virological characteristics of SARS-CoV-2 BA.2 variant

Yamasoba

Kimura

Nasser

et al. 2022

Preprint

113

224

View full text Add to dashboard Cite

Soon after the emergence and global spread of a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron lineage, BA.1 (ref1, 2), another Omicron lineage, BA.2, has initiated outcompeting BA.1. Statistical analysis shows that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralisation experiments show that the vaccine-induced humoral immunity fails to function against BA.2 like BA.1, and notably, the antigenicity of BA.2 is different from BA.1. Cell culture experiments show that BA.2 is more replicative in human nasal epithelial cells and more fusogenic than BA.1. Furthermore, infection experiments using hamsters show that BA.2 is more pathogenic than BA.1. Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1.

show abstract

“…Molnupiravir inhibited SARS-CoV-2 in cell culture assays, with 50% effective concentrations (EC 50 ) ranging between 0.32 and 2.66 µM [7]. Molnupiravir has broad-spectrum in vitro activity against SARS-CoV-2 variants of concern such as B1.1.529 (omicron) [21][22][23][24][25][26], and B.1.1.7 (alpha), B.1351 (beta), P.1 (gamma) and B.1.617.2 (delta) [7]. The EC 50 values were 1.86-1.95 μM [21], and 1.59, 1.77, 1.32 and 1.68 μM [7], respectively.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Molnupiravir: First Approval

Syed

2022

Drugs

View full text Add to dashboard Cite

Molnupiravir (Lagevrio ® ) is an orally-administered antiviral prodrug that inhibits replication of RNA viruses through viral error induction. It is being developed by Merck and Ridgeback Biotherapeutics for the prevention and treatment of Coronavirus disease 2019 (COVID-19). Molnupiravir received its first approval on 4 November 2021 in the UK for the treatment of mild to moderate COVID-19 in adults with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic test and who have at least one risk factor for developing severe illness. Molnupiravir is filed for approval and has emergency use authorization for the treatment of COVID-19 in several countries, including the USA, Japan and those in the EU. This article summarizes the milestones in the development of molnupiravir leading to this first approval for COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-022-01684-5.

show abstract

Efficacy of Antibodies and Antiviral Drugs against Covid-19 Omicron Variant

Cited by 369 publications

References 4 publications

Characterization and antiviral susceptibility of SARS-CoV-2 Omicron/BA.2

Characterization and antiviral susceptibility of SARS-CoV-2 Omicron/BA.2

Virological characteristics of SARS-CoV-2 BA.2 variant

Molnupiravir: First Approval

Contact Info

Product

Resources

About