Delving into the Latest Updates on SARS-CoV-2 project 2(AbSano) with Synapse

Overview

Basic Info

Drug Type

Antibody

Synonyms-

Target

SARS-CoV-2 S protein

Mechanism

SARS-CoV-2 S protein modulators(SARS-CoV-2 S protein modulators)

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication

COVID-19

Inactive Indication-

Originator Organization

AbSano

Active Organization

AbSano

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Plasmids encoding wildtype SP or empty vector (p3.1) were transfected into COS-7 cells, and cell lysates were prepared as a reservoir for SP or p3.1 (control), respectively. K18-hACE2^TG and K18-hACE2^TG/Tymp^-/- mice were treated with a single dose of SP or p3.1 by intraperitoneal injection and then subjected to thrombosis studies three days later. The role of SP on inflammatory signaling activation was assessed in BEAS-2B cells.

RESULTS:

SARS-CoV-2 SP increased the expression of TYMP, resulting in the activation of STAT3 and NF-κB in BEAS-2B cells. A siRNA-mediated knockdown of TYMP attenuated SP-enhanced activation of STAT3. SP significantly promoted arterial thrombosis in K18-hACE2^TG mice. SP-accelerated thrombosis was attenuated by inhibition or genetic ablation of TYMP. SP treatment did not influence ADP- or collagen-induced platelet aggregation but significantly increased platelet adhesion to fibrinogen. SP treatment also significantly shortened activated partial thromboplastin time, which was reversed and even prolonged by TYMP deficiency. Additionally, SP binds to platelet factor 4 (PF4) and TYMP. TYMP does not bind PF4 but enhances the formation of the SP/PF4 complex, which may augment the procoagulant and prothrombotic effect of PF4.

CONCLUSIONS:

We conclude that SP is prothrombotic and upregulates TYMP expression, and TYMP inhibition or knockout mitigates SP-enhanced thrombosis. These findings suggest that inhibition of TYMP may be a novel therapeutic strategy for COVID-19-associated thrombosis.

01 Oct 2024·CLINICAL MICROBIOLOGY AND INFECTION

Neurodevelopmental outcomes of infants after in utero exposure to SARS-CoV-2 or mRNA-COVID-19 vaccine compared with unexposed infants: a COVI-PREG prospective cohort study

Article

Author: Madec, Yoann ; Graz, Myriam Bickle ; Bromley, Rebecca L ; Favre, Guillaume ; Panchaud, Alice ; Blume, Carolin ; Baud, David ; Bromley, Rebecca L. ; Daire, Charlotte ; Radan, Anda-Petronela ; Surbek, Daniel ; Winterfeld, Ursula ; Kalimeris, Stylianos ; Schneider, Juliane ; Raio, Luigi ; Bluett-Duncan, Matthew ; Maisonneuve, Emeline ; Pomar, Léo

OBJECTIVES:

Data are lacking regarding the long-term consequences of SARS-CoV-2 and COVID-19 mRNA vaccine on infants exposed in utero. We aimed to evaluate the neurodevelopment of infants exposed prenatally to SARS-CoV-2 or mRNA-COVID-19 vaccine during pregnancy at 12 months after birth.

METHODS:

Infants born from mothers exposed to SARS-CoV-2 or mRNA-COVID-19 vaccine during pregnancy, or unexposed to either the virus or the vaccine were enrolled from 2021 to 2023. Infants with prenatal exposure to the virus or vaccine were compared to infants without prenatal exposure to the virus and/or vaccine. Parents received a neurodevelopmental questionnaire (ASQ-3) at 12 months after birth assessing 5 subdomains: communication, gross motor, fine motor, problem solving and personal social development. A low score was defined as <2 standard deviations below the normative mean in at least one of the subdomains.

RESULTS:

A total of 330 infants were included (76 in the SARS-CoV-2 group; 153 in the mRNA-COVID-19 vaccine group; 101 in the reference group). In utero exposure to SARS-CoV-2 or mRNA-COVID-19 vaccine were not associated with an increased risk of a low score for at least one subdomain compared to the reference group. The crude odds ratios were 1.16 (95% confidence interval [CI] 0.59-2.28) and 1.04 (95% CI 0.58-1.86), respectively. Results remained consistent in the multivariate analysis, showing no increased risk of a low score for at least one subdomain for infants exposed to SARS-CoV-2 or mRNA-COVID-19 vaccine, compared to the reference group. The adjusted odds ratios were 1.74 (95% CI 0.76-3.99) and 0.76 (95% CI 0.39-1.49), respectively.

CONCLUSION:

In utero exposure to SARS-CoV-2 or mRNA-COVID-19 vaccine was not associated with an increased risk of a low score for at least one ASQ-3 subdomain at 12 months after birth. Additional studies are needed to confirm our results, especially longer-term evaluation of infant development.

15 May 2024·JOURNAL OF CELL SCIENCE

SARS-CoV-2 NSP5 antagonizes MHC II expression by subverting histone deacetylase 2

Article

Author: Jung, Catherine ; Lac, Alex ; Dickson, Brandon H. ; Aktar, Amena ; Fink, Corby ; Vrieze, Angela M. ; Guo, Peter N. ; Taefehshokr, Nima ; Heit, Bryan ; Dikeakos, Jimmy D. ; Blythe, Eoin N. ; Dekaban, Gregory A.

ABSTRACT:

SARS-CoV-2 interferes with antigen presentation by downregulating major histocompatibility complex (MHC) II on antigen-presenting cells, but the mechanism mediating this process is unelucidated. Herein, analysis of protein and gene expression in human antigen-presenting cells reveals that MHC II is downregulated by the SARS-CoV-2 main protease, NSP5. This suppression of MHC II expression occurs via decreased expression of the MHC II regulatory protein CIITA. CIITA downregulation is independent of the proteolytic activity of NSP5, and rather, NSP5 delivers HDAC2 to the transcription factor IRF3 at an IRF-binding site within the CIITA promoter. Here, HDAC2 deacetylates and inactivates the CIITA promoter. This loss of CIITA expression prevents further expression of MHC II, with this suppression alleviated by ectopic expression of CIITA or knockdown of HDAC2. These results identify a mechanism by which SARS-CoV-2 limits MHC II expression, thereby delaying or weakening the subsequent adaptive immune response.

100 Deals associated with SARS-CoV-2 project 2(AbSano)

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