chuka_lis (chuka_lis) wrote,
chuka_lis
chuka_lis

Вырисовывается

К вопросу о штаммах.
Поскольку коронавирусу на человеческом поле есть где развернуться- а эволюция это процесс, то часть из мутаций не могла не оказаться "более выгодной", позволяя вирусу наиболее эффективно осваивать новый ресурс.
Вышли 2 статьи примерно об одном и том же (разные команды изучают, с разных сторон, и порой приходят к выводам почти одновременно)

Spike glycoprotein and host cell determinants of SARS-CoV-2 entry and cytopathic effects
и
SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility
 (по ссылкам есть пдф)
Мутация, приведшая к небольшим изменениям на участке шипикового белка S - D614G - позволяет коронавиурсу лучше проникать в клетки эпителия верхних дыхательных путей, лучше размножаться внутри клеток и передаваться дальше, и, так же, вирус с ней обладает достаточным цитопатическим эффектом. За счет большей заразности этот штамм хорошо распространен и в последнее время стал выделяться все чаще и чаще.

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SARS-CoV-2, a betacoronavirus, is the cause of the COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein trimer mediates virus entry into host cells and cytopathic effects. We studied the contribution of several S glycoprotein features to these functions, focusing on those that differ among related coronaviruses. Acquisition of the furin cleavage site by the SARS-CoV-2 S glycoprotein decreased virus stability and infectivity, but greatly enhanced the ability to form lethal syncytia. Notably, the D614G change found in globally predominant SARS-CoV-2 strains restored infectivity, modestly enhanced responsiveness to the ACE2 receptor and susceptibility to neutralizing sera, and tightened association of the S1 subunit with the trimer. Apparently, two unique features of the SARS-CoV-2 S glycoprotein, the furin cleavage site and D614G, have evolved to balance virus infectivity, stability, cytopathicity and antibody vulnerability. Although the endodomain (cytoplasmic tail) of the S2 subunit was not absolutely required for virus entry or syncytium formation, alteration of palmitoylated cysteine residues in the cytoplasmic tail decreased the efficiency of these processes. As proteolytic cleavage contributes to the activation of the SARS-CoV-2 S glycoprotein, we evaluated the ability of protease inhibitors to suppress S glycoprotein function. Matrix metalloprotease inhibitors suppressed S-mediated cell-cell fusion, but not virus entry. Synergy between inhibitors of matrix metalloproteases and TMPRSS2 suggests that both proteases can activate the S glycoprotein during the process of syncytium formation. These results provide insights into SARS-CoV-2 S glycoprotein-host cell interactions that likely contribute to the transmission and pathogenicity of this pandemic agent.

и

During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic. However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human ACE2, (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro, it provides a real competitive advantage in vivo, particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating.
Tags: биология, коронавирус, статьи
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