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  • Review: Efficacy of...

Review: Efficacy of Antiviral Agents Against Omicron Subvariant BA.2

Dr. Kamal Kant KohliWritten by Dr. Kamal Kant Kohli Published On 2022-05-16T11:45:32+05:30  |  Updated On 2022-05-16T13:11:49+05:30
Review: Efficacy of Antiviral Agents Against  Omicron Subvariant BA.2
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The omicron (B.1.1.529) variant of SARS-CoV-2, has spread rapidly around the world and has already become the predominant variant circulating in many countries. Most circulating omicron variants belong to sublineage BA.1; however, in Denmark, India, and the Philippines, the sublineage BA.2 is now becoming dominant. The BA.2 and BA.1 variants share 12 of these 16 substitutions; however, BA.2 has four substitutions in the receptor-binding domain (i.e., S371F, T376A, D405N, and R408S) that differ from those in BA.1. These findings suggest that there may be differences in the effectiveness of monoclonal antibodies against these different omicron sublineages.

The current study examined the neutralizing ability of therapeutic monoclonal antibodies individually and in combination, against the omicron BA.2 subvariant. The results are as followed;

  • A live-virus focus reduction neutralization test (FRNT) showed that both etesevimab and bamlanivimab, individually and in combination, lost neutralizing activity against omicron/BA.2.
  • However, imdevimab was previously shown to lose neutralizing activity against omicron/BA.1 (NC928) and omicron/BA.1.1 (NC929), had neutralizing activity against omicron/BA.2 (NCD1288).
  • In addition, the combination of imdevimab and casirivimab also inhibited omicron/BA.2 but did not inhibit omicron/BA.1 or omicron/BA.1.1.
  • However, the FRNT50 (the titer of monoclonal antibodies required for a 50% reduction in the number of infectious foci) value of this combination therapy was higher by a factorof43.0 to 143.6 for omicron/BA.2 than for an ancestral strain and other variants of concern (i.e., the alpha [B.1.1.7], beta [B.1.351], gamma [P.1], and delta [B.1.617.2] variants).
  • S309 (the precursor of sotrovimab), which has been shown to have lower neutralizing activity against omicron/BA.1 and omicron/BA.1.1 than against the ancestral strain and other variants of concern had even less neutralizing activity against omicron/BA.2.
  • The susceptibilities of omicron/BA.2 (NCD1288) to remdesivir, molnupiravir, and nirmatrelvir were similar to those of the ancestral strain and other variants of concern.

Table: Efficacy of Monoclonal Antibodies and Antiviral Drugs against the Omicron/BA.2 Subvariant in Vitro

Monoclonal Antibody or Antiviral Drug

hCov-19/Japan/UT-NCD1288-2N/2022 (Omicron/BA.2)

Tested Value

Factor Increase as Compared with the Ancestral Strain

Neutralization activity of monoclonal antibody†

LY-CoV016, etesevimab

>50,000 ng/ml

>2749

LY-CoV0555, bamlanivimab

>50,000 ng/ml

>10,661

REGN10987, imdevimab

68.65±8.84 ng/ml

22.5

REGN10933, casirivimab

1666.19±771.77 ng/ml

597.2

COV2-2196, tixagevimab

395.78±62.37 ng/ml

206.1

COV2-2130, cilgavimmab

4.44±2.72 ng/ml

0.6

S309, sotrovimab precusor

1359.05±269.23 ng/ml

49.7

LY-CoV016 plus LY-CoV555

>10,000 ng/ml

>794

REGN10987 plus REGN10933

222.59±64.47 ng/ml

63.1

COV2-2196 plus COV-2130

14.48±2.04 ng/ml

4.2


Viral susceptiblity to drug‡

GS-441525§

2.85±0.31чM

2.7

EIDD-1931¶

067±0.22чM

1.3

PF-07321332§

6.76±0.69чM

1.9


* Plus-minus values are means ±SD. The antibodies used in this analysis were produced in the authors; laboratory and are not identical to the commercially available products. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant is denoted according to the World Health Organization labels for the Pango lineage.

† The individual monoclonal antibodies were tested at a starting concentration of 50,000 ng per milliliter as a 50% focus reduction neutralization test (FRNT50) titer. The monoclonal antibody combinations were tested at a starting concentration of 10,000 ng per milliliter for each antibody. Shown is the factor increase in the FRNT50 titers of monoclonal antibodies against the omicron/BA.2 subvariant as compared with that against the ancestral strain, SARS- CoV-2/UT-NC002-1T/Human/2020/Tokyo (A.)

‡ In this category, the value is the 50% inhibitory concentration (Ic50) of the mean micromole value of triplicate reactions. The factor increase in the Ic50 of drugs against the omicron/BA.2 subvariant as compared with that against the ancestral strain, SARS-CoV-2/UT-NC002-1T/HUman/2020/Tokyo (A), are shown.

§ GS-441524 is the main metabolite of remdesivir, an RNA-dependent RNA polymerase inhibitor.

¶ EIDD-1931 is the active form of molnupiravir, an RNA-dependant RNA polymerase inhibitor.

|| PF-07321332 (also know as nirmatrelvir) is a protease inhibitor.


Reference:

Takashita E, Kinoshita N, Yamayoshi S, Sakai-Tagawa Y, Fujisaki S, Ito M, Iwatsuki-Horimoto K, Halfmann P, Watanabe S, Maeda K, Imai M, Mitsuya H, Ohmagari N, Takeda M, Hasegawa H, Kawaoka Y. Efficacy of Antiviral Agents against the SARS-CoV-2 Omicron Subvariant BA.2. N Engl J Med. 2022 Apr 14;386(15):1475-1477. doi: 10.1056/NEJMc2201933

To know more about prescribing information, click here.

Disclaimer: This content and information provided are intended for update strictly for Registered Medical Practitioners/ Physicians treating Covid 19 only. The information mentioned herein is not intended nor implied to be a substitute for professional medical advice. Any advice regarding the management of any medical condition is totally at the discretion of the doctor (Registered Medical Practitioner)/ physician treating Covid 19 patients. Prescription of the drug is the prerogative of doctors (Registered Medical Practitioner/ Physician treating Covid 19) at his /her sole discretion. Physicians treating Covid 19 patients must refer to the full prescribing information of the product for use of the product. Copying, reproduction, and circulation of the information published herein in any form or by any means either mechanically/ print or electronically without prior consent is strictly prohibited. Any unauthorized person having possession of this document should discard the same or inform/ notify/ return it to Cipla Ltd. To report any adverse events/special situations with Cipla medicinal products email drugsafety@cipla.com. or via the national Pharmacovigilance Programme of India by calling on 1800267 7779 (Cipla number) or you can report to PvPI on 1800 180 3024. By reporting side effects, you can help provide more information on the safety of this product. For complete prescribing information, please login www.ciplamed.com

imdevimab casirivimab casirivimab-imdevimab antibody cocktail ronapreve omicron ba1 omicron sublineage SARS COV2 REGEN COV 
Dr. Kamal Kant Kohli
Dr. Kamal Kant Kohli

    Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as an Editor-in-Chief for the Speciality Medical Dialogues section. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Before Joining Medical Dialogues, he has served at important positions in the medical industry in India including as the Hony. Secretary of the Delhi Medical Association as well as the chairman of Anti-Quackery Committee in Delhi and worked with other Medical Councils in India. Email: editorial@medicaldialogues.in. Contact no. 011-43720751

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