Thursday, March 28, 2024
Thursday, March 28, 2024
HomePet NewsSmall Pets NewsCharacterization of SARS-CoV-2 Omicron BQ.1.1

Characterization of SARS-CoV-2 Omicron BQ.1.1

Date:

Related stories

-Advertisement-spot_img
-- Advertisment --
- Advertisement -

In a recent study posted to the bioRxiv* preprint server, researchers characterized the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BQ.1.1 sub-variant.

Study: Convergent evolution of the SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant. Image Credit: Naeblys/Shutterstock
Study: Convergent evolution of the SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant. Image Credit: Naeblys/Shutterstock

Background

SARS-CoV-2 Omicron BA.1 rapidly supplanted the Delta variant, and shortly after, Omicron BA.2 was the predominant variant. After that, numerous BA.2 descendants emerged, including BA.2.75 and BA.5. Although BA.2.75 and BA.5 diverged from BA.2, they are phylogenetically independent, and recent studies report similar evolutionary patterns in the spikes of BA.2.75 and BA.5 sub-variants.

Previously, the authors reported an increase in the pathogenicity of BA.2.75 and BA.5 sub-variants in a hamster model relative to the BA.2 sub-variant, suggesting that the sub-variants evolved to enhance intrinsic pathogenicity. Despite the emergence of several new sub-variants after BA.5, they have failed to outcompete BA.5.

Instead, the emergent sub-variants appear to be under convergent evolution, acquiring amino acid substitutions at the same site. The BQ.1.1 sub-variant, a descendant of BA.5, harbors five convergent substitutions (R346T, K444T, L452R, N460K, and F486V) and has been classified as a variant under monitoring by the World Health Organization (WHO).

The study and findings

In the present study, researchers explored the evolutionary characteristics underlying the convergent evolution of SARS-CoV-2 Omicron lineages. First, they constructed phylogenetic trees for Omicron sub-variants to identify where convergent substitutions occurred. The L452 residue had the highest substitution frequency in the BA.2 lineage. Moreover, substitution events were relatively more frequent in newer lineages than BA.1/2.

Next, the authors modeled the relationship between spike substitutions and viral epidemic dynamics to assess the impact of substitutions on viral fitness. They analyzed a dataset of more than 300,000 Omicron sequences collected between March 1, 2022, and October 15, 2022, that included 254 spike haplotypes. The five convergent substitutions positively affected the effective reproductive number (Re).

Moreover, the spike haplotype corresponding to the BQ.1.1 sub-variant had the highest Re. Further investigations indicated that viral fitness increased independently in multiple Omicron lineages during BA.5 diversification. The analysis also suggested that BQ.1.1 increased its fitness by serially acquiring K444T, N460K, and R346T substitutions.

The researchers examined the immune resistance of SARS-CoV-2 Omicron BQ.1.1 using pseudoviruses and observed that BA.5 and BQ.1.1 were markedly resistant to neutralization by Omicron BA.2 breakthrough infection sera. Notably, BQ.1.1 showed 2.7-fold increased resistance to breakthrough infection sera relative to BA.5. Similarly, BQ.1.1 was 5.6-fold more resistant to BA.5 infection sera than BA.5.

Sera from hamsters infected with BA.2, BA.2.75, or BA.5 exhibited high antiviral activity against the infecting variant but lacked cross-reactivity against other variants. Yeast surface display (YSD) assay showed that the dissociation constant (KD) of BQ.1.1 spike’s receptor-binding domain (RBD) to human angiotensin-converting enzyme 2 (hACE2) was significantly lower than that of BA.5 spike RBD, implying a higher affinity of BQ.1.1 spike to hACE2 than BA.5 spike.

The N460K and R346T substitutions in BQ.1.1 spike were implicated in the significantly enhanced binding affinity. Further, BQ.1.1 pseudovirus showed higher infectivity than BA.2 or BA.5 pseudovirus. The R346T and N460K substitutions of the BQ.1.1 spike were responsible for the increased infectivity. Syrian hamsters were infected with clinical isolates of Delta, BA.5, or BQ.1.1.

The pulmonary function of hamsters was determined based on the ratio of time to peak expiratory flow relative to total expiratory time (Rpef) and enhanced pause (Penh). Delta infection caused significant changes in these parameters than BA.5 infection, suggesting that Delta was more pathogenic than BA.5. 

The Rpef and Penh of BQ.1.1-infected hamsters were significantly higher and lower than those of BA.5-infected animals, respectively. This meant that the pathogenicity of BQ.1.1 was comparable to or even lower than that of BA.5. Viral RNA load in the lungs of BA.5-infected hamsters was similar to that of hamsters infected with Delta or Omicron BQ.1.1.

Finally, the authors examined the intrinsic pathogenicity of SARS-CoV-2 Omicron BQ.1.1 by analyzing the right lung of infected hamsters and scoring five histopathological features/parameters – 1) bronchitis/bronchiolitis, 2) hemorrhage with congestive edema, 3) alveolar damage, 4) hyperplasia of type II pneumocytes, and 5) the area of hyperplasia.

Delta-infected hamsters had a significantly higher cumulative histopathological score than BA.5-infected animals. In contrast, the aggregate scores were comparable between hamsters infected with BA.5 and BQ.1.1, although BQ.1.1-infected animals showed enhanced bronchitis/bronchiolitis and more type II pneumocytes.

Conclusions

To summarize, the authors uncovered the convergent evolution of sub-Omicron variants, highlighting the frequent substitutions at five sites in the viral spike protein that improved viral fitness and Re. SARS-CoV-2 Omicron BQ.1.1, which harbors all five convergent substitutions, showed the highest Re. The BQ.1.1 sub-variant was also highly resistant to neutralization by BA.2 or BA.5 breakthrough infection sera and showed high binding affinity to hACE2 and greater fusogenicity than BA.5.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

- Advertisement -
Pet News 2Day
Pet News 2Dayhttps://petnews2day.com
About the editor Hey there! I'm proud to be the editor of Pet News 2Day. With a lifetime of experience and a genuine love for animals, I bring a wealth of knowledge and passion to my role. Experience and Expertise Animals have always been a central part of my life. I'm not only the owner of a top-notch dog grooming business in, but I also have a diverse and happy family of my own. We have five adorable dogs, six charming cats, a wise old tortoise, four adorable guinea pigs, two bouncy rabbits, and even a lively flock of chickens. Needless to say, my home is a haven for animal love! Credibility What sets me apart as a credible editor is my hands-on experience and dedication. Through running my grooming business, I've developed a deep understanding of various dog breeds and their needs. I take pride in delivering exceptional grooming services and ensuring each furry client feels comfortable and cared for. Commitment to Animal Welfare But my passion extends beyond my business. Fostering dogs until they find their forever homes is something I'm truly committed to. It's an incredibly rewarding experience, knowing that I'm making a difference in their lives. Additionally, I've volunteered at animal rescue centers across the globe, helping animals in need and gaining a global perspective on animal welfare. Trusted Source I believe that my diverse experiences, from running a successful grooming business to fostering and volunteering, make me a credible editor in the field of pet journalism. I strive to provide accurate and informative content, sharing insights into pet ownership, behavior, and care. My genuine love for animals drives me to be a trusted source for pet-related information, and I'm honored to share my knowledge and passion with readers like you.
-Advertisement-

Latest Articles

-Advertisement-

LEAVE A REPLY

Please enter your comment!
Please enter your name here
Captcha verification failed!
CAPTCHA user score failed. Please contact us!