ABSTRACT
The Covid-19 variants' transmissibility was further quantitatively analyzed in silico to study the binding strength with ACE-2 and find the binding inhibitors. The molecular interaction energy values of their optimized complex structures (MIFS) demonstrated that Omicron BA.4 and 5's MIFS value (344.6 kcal mol-1) was equivalent to wild-type MIFS (346.1 kcal mol-1), that of Omicron BQ.1 and BQ. 1.1's MIFS value (309.9 and 364.6 kcal mol-1). Furthermore, the MIFS value of Omicron BA.2.75 (515.1 kcal mol-1) was about Delta-plus (511.3 kcal mol-1). The binding strength of Omicron BA.4, BA. 5, and BQ.1.1 may be neglectable, but that of Omicron BA.2.75 was urging. Furthermore, the 79 medicine candidates were analyzed as the binding inhibitors from binding strength with ACE-2. Only carboxy compounds were repulsed from the ACE-2 binding site indicating that further modification of medical treatment candidates may produce an effective binding inhibitor.
ABSTRACT
Limited data are available on the effectiveness of COVID-19 vaccines used in China in real-world outbreaks - especially against Omicron variants in vaccinated individuals. Two outbreaks of SARS-CoV-2 Omicron variants - the first involving the sub-lineage BA.2 and the second the BA.1 variant - occurred in Quzhou. Infected people and their close contacts were divided according to vaccination status: unvaccinated, partially vaccinated, fully vaccinated, and boosted. The Cox proportional-hazard regression model was used to estimate the evolving hazard for vaccinated individuals after their first immunization. 138 people had been infected with the SARS-CoV-2 Omicron BA.2 variant and 13 with the BA.1 variant. Of the 151 infections, 99.34% (150/151) were mild or asymptomatic and 90.07% (136/151) were vaccine breakthrough cases. The total vaccine effectiveness (VE) of partial, full, and booster vaccinations during the two outbreaks was 47.4% (95%CI: 0-93.1%), 28.9% (95%CI: 0-60.2%), and 27.5% (95%CI: 0-58.3%). The VE of booster vaccination against the Omicron BA.1 variant was higher than that for the BA.2 variant. The cumulative hazard began to increase 220 days after the first immunization. The transmissibility of the Omicron BA.2 variant as for BA.1 did not increase in vaccinated individuals; booster vaccination after a primary course substantially increased protection. Our study found that the SARS-CoV-2 Omicron variant caused less severe illness and that the VE of boosters against the Omicron variant was less than 30%. Timely administration of the booster dose was important, especially for individuals aged over 80 years old.
Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , Aged, 80 and over , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Disease Outbreaks/prevention & controlABSTRACT
The SARS-CoV-2 Omicron variants were first detected in November 2021, and several Omicron lineages (BA.1, BA.2, BA.3, BA.4, and BA.5) have since rapidly emerged. Studies characterizing the mechanisms of Omicron variant infection and sensitivity to neutralizing antibodies induced upon vaccination are ongoing by several groups. In the present study, we used pseudoviruses to show that the transmembrane serine protease 2 (TMPRSS2) enhances infection of BA.1, BA.1.1, BA.2, and BA.3 Omicron variants to a lesser extent than ancestral D614G. We further show that Omicron variants have higher sensitivity to inhibition by soluble angiotensin-converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G. The Omicron variants also more efficiently used ACE2 receptors from 9 out of 10 animal species tested, and unlike the D614G variant, used mouse ACE2 due to the Q493R and Q498R spike substitutions. Finally, neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7- to 8-fold less potent than the D614G. These results provide insights into the transmissibility and immune evasion capacity of the emerging Omicron variants to curb their ongoing spread. IMPORTANCE The ongoing emergence of SARS-CoV-2 Omicron variants with an extensive number of spike mutations poses a significant public health and zoonotic concern due to enhanced transmission fitness and escape from neutralizing antibodies. We studied three Omicron lineage variants (BA.1, BA.2, and BA.3) and found that transmembrane serine protease 2 has less influence on Omicron entry into cells than on D614G, and Omicron exhibits greater sensitivity to endosomal entry inhibition compared to D614G. In addition, Omicron displays more efficient usage of diverse animal species ACE2 receptors than D614G. Furthermore, due to Q493R/Q498R substitutions in spike, Omicron, but not D614G, can use the mouse ACE2 receptor. Finally, three doses of Pfizer/BNT162b2 mRNA vaccination elicit high neutralization titers against Omicron variants, although the neutralization titers are still 7- to 8-fold lower those that against D614G. These results may give insights into the transmissibility and immune evasion capacity of the emerging Omicron variants to curb their ongoing spread.