Thread by @NavroopSingh_

Ineffective neutralization of the SARS-CoV-2 Mu variant by convalescent and vaccine sera biorxiv.org/content/10.110…

Here, we demonstrate that the Mu variant is highly resistant to sera from COVID-19 convalescents and BNT162b2-vaccinated individuals. Direct comparison of different SARS-CoV-2 spike proteins revealed that Mu spike is more resistant to serum-mediated neutralization than all other

currently recognized variants of interest (VOI) and concern (VOC). This includes the Beta variant (B.1.351) that has been suggested to represent the most resistant variant to convalescent and vaccinated sera to date (e.g., Collier et al, Nature, 2021; Wang et al, Nature, 2021)

Our results will help to better assess the risk posed by the Mu variant for vaccinated, previously infected and naïve populations. [If MU is worse than BETA then god bless us coz most Spike Vaccines performed very poorly against BETA even compared to Delta].

The majority of Mu variants harbors the following eight mutations in spike: T95I, YY144-145TSN, R346K, E484K, N501Y, D614G, P681H, and D950N (Tables S3 and S4). These include mutations commonly identified in VOCs: E484K (shared with Beta, Gamma), N501Y (shared with Alpha),

P681H (shared with Alpha) and D950N (shared with Delta) (Table S5). Of those, the E484K change has been shown to reduce sensitivity towards antibodies induced by natural SARS-CoV-2 infection and vaccination.

To assess the sensitivity of the Mu variant to antibodies induced by SARS CoV-2 infection and vaccination (Pfizer), we generated pseudoviruses harboring the spike proteins of Mu or the other VOC/VOIs.

Virus neutralization assays revealed that the Mu variant is 12.4-fold more resistant to sera of eight COVID-19 convalescents, who were infected during the early pandemic (April–September, 2020), than the parental
virus (P=0.0078). [Holy SHIT 🤯]

Also, the Mu variant was 7.6-fold more resistant to sera obtained from ten BNT162b2-vaccinated individuals compared to the parental virus (P=0.0020).

Notably, although the Beta VOC was thought to be the most resistant variant to date,3,4 Mu pseudoviruses were significantly more resistant to convalescent serum-mediated neutralization than Beta pseudoviruses.

Thus, the Mu variant shows a pronounced resistance to antibodies elicited by natural SARS-CoV-2 infection and the BNT162b2 mRNA vaccine. Since breakthrough infections are a major threat of newly emerging SARS-CoV-2 75 variants.

we strongly suggest to further characterize and monitor the Mu variant.