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1.
J Comput Aided Mol Des ; 37(12): 585-606, 2023 12.
Article in English | MEDLINE | ID: mdl-37792106

ABSTRACT

Herein, we conducted simulations of trimeric Spike from several SARS-CoV-2 variants of concern (Delta and Omicron sub-variants BA.2, BA.5, and BQ.1) and investigated the mechanisms by which specific mutations confer resistance to neutralizing antibodies. We observed that the mutations primarily affect the cooperation between protein domains within and between protomers. The substitutions K417N and L452R expand hydrogen bonding interactions, reducing their interaction with neutralizing antibodies. By interacting with nearby residues, the K444T and N460K mutations in the SpikeBQ.1 variant potentially reduces solvent exposure, thereby promoting resistance to antibodies. We also examined the impact of D614G, P681R, and P681H substitutions on Spike protein structure that may be related to infectivity. The D614G substitution influences communication between a glycine residue and neighboring domains, affecting the transition between up- and -down RBD states. The P681R mutation, found in the Delta variant, enhances correlations between protein subunits, while the P681H mutation in Omicron sub-variants weakens long-range interactions that may be associated with reduced fusogenicity. Using a multiple linear regression model, we established a connection between inter-protomer communication and loss of sensitivity to neutralizing antibodies. Our findings underscore the importance of structural communication between protein domains and provide insights into potential mechanisms of immune evasion by SARS-CoV-2. Overall, this study deepens our understanding of how specific mutations impact SARS-CoV-2 infectivity and shed light on how the virus evades the immune system.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Humans , Hydrogen Bonding , Linear Models , Mutation
2.
Virus Res ; 334: 199169, 2023 09.
Article in English | MEDLINE | ID: mdl-37406934

ABSTRACT

The largest wave of infection with SARS-CoV-2 virus in Ecuador was observed in mid-December 2021 and early January 2022, driven by B.1.1.529/BA (Omicron) variant. During the second half of March, an increase in the number of daily cases was observed and coincided with the emergence of the BA.2 variant, which we describe in the present study. The first sequenced five cases of SARS-CoV-2 21L/BA.2 in Ecuador were identified using variant specific genotyping by qPCR and confirmed by whole genome sequencing (WGS). The first sequenced Ecuadorian BA.2 isolate was obtained from a person with international travel history who became symptomatic 3 days after travelling, whereas in the other cases no travel history was recorded.


Subject(s)
COVID-19 , Humans , Ecuador , COVID-19/epidemiology , SARS-CoV-2/genetics , Base Sequence , Whole Genome Sequencing
3.
Braz J Microbiol ; 54(3): 1847-1851, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37269428

ABSTRACT

Since the beginning of the SARS-CoV-2 pandemic, studies on the variants and sublineages stand out, mainly in the cases of reinfection in a short period. In this study, we describe a case of infection by BA.1.1 sublineage in an individual from Southern Brazil. The same patient acquired reinfection with sublineage BA.2 within 16 days after the first detection. The viral extraction and RT-qPCR were performed on the samples LMM72045 (collected in May 2022) and LMM72044 (collected in June 2022). After the confirmation of SARS-CoV-2 infection, we conducted the sequencing and viral genome analysis. This case of reinfection affected a 52-year-old male patient, without comorbidities, with three doses of vaccines against COVID-19, showing symptoms on May 19. These symptoms lasted for approximately six days. The patient returned to work activities on May 30. However, on June 4, the patient felt a new round of clinical signs that lasted for approximately seven days. Analysis of the viral genomes recovered from patients' clinical samples revealed that the two COVID-19 episodes were related to two divergent VOC Omicron sublineages, namely, BA.1.1 for the first round of symptoms and BA.2 for the second infection. Based on our findings, we can say that the present case of reinfection is the shortest described so far.


Subject(s)
COVID-19 , SARS-CoV-2 , Male , Humans , Middle Aged , SARS-CoV-2/genetics , COVID-19/diagnosis , Reinfection , COVID-19 Vaccines , Brazil/epidemiology
4.
Viruses ; 15(2)2023 01 22.
Article in English | MEDLINE | ID: mdl-36851525

ABSTRACT

The COVID-19 pandemic has lately been driven by Omicron. This work aimed to study the dynamics of SARS-CoV-2 Omicron lineages during the third and fourth waves of COVID-19 in Argentina. Molecular surveillance was performed on 3431 samples from Argentina, between EW44/2021 and EW31/2022. Sequencing, phylogenetic and phylodynamic analyses were performed. A differential dynamic between the Omicron waves was found. The third wave was associated with lineage BA.1, characterized by a high number of cases, very fast displacement of Delta, doubling times of 3.3 days and a low level of lineage diversity and clustering. In contrast, the fourth wave was longer but associated with a lower number of cases, initially caused by BA.2, and later by BA.4/BA.5, with doubling times of about 10 days. Several BA.2 and BA.4/BA.5 sublineages and introductions were detected, although very few clusters with a constrained geographical distribution were observed, suggesting limited transmission chains. The differential dynamic could be due to waning immunity and an increase in population gatherings in the BA.1 wave, and a boosted population (for vaccination or recent prior immunity for BA.1 infection) in the wave caused by BA2/BA.4/BA.5, which may have limited the establishment of the new lineages.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , Argentina/epidemiology , Pandemics , Phylogeny
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