Biochemical and Biophysical Research Communications, Год журнала: 2021, Номер 574, С. 14 - 19
Опубликована: Авг. 15, 2021
Язык: Английский
Cell, Год журнала: 2021, Номер 184(19), С. 4848 - 4856
Опубликована: Авг. 19, 2021
Язык: Английский
Процитировано
454
Cell, Год журнала: 2022, Номер 185(5), С. 860 - 871.e13
Опубликована: Янв. 25, 2022
The SARS-CoV-2 Omicron variant with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures the spike (S) from reveals amino acid substitutions forging interactions that stably maintain an active conformation for receptor recognition. relatively more compact domain organization confers improved stability and enhances attachment but compromises efficiency viral fusion step. Alterations in local conformation, charge, hydrophobic microenvironments underpin modulation epitopes such they are not recognized by most NTD- RBD-antibodies, facilitating immune escape. Structure S bound human ACE2, together analysis sequence conservation ACE2 binding region 25 sarbecovirus members, as well heatmaps immunogenic sites their corresponding mutational frequencies, sheds light on conserved structurally restrained regions can be used development broad-spectrum vaccines therapeutics.
Язык: Английский
Процитировано
389
npj Vaccines, Год журнала: 2021, Номер 6(1)
Опубликована: Авг. 16, 2021
COVID-19 vaccines were developed with an unprecedented pace since the beginning of pandemic. Several them have reached market authorization and mass production, leading to their global application on a large scale. This enormous progress was achieved fundamentally different vaccine technologies used in parallel. mRNA, adenoviral vector as well inactivated whole-virus are now widespread use, subunit is final stage authorization. They all rely native viral spike protein (S) SARS-CoV-2 for inducing potently neutralizing antibodies, but presentation this key antigen immune system differs substantially between categories vaccines. In article, we review relevance structural modifications S modes expression after vaccination genetic adenovirus-vector mRNA Distinguishing characteristics unknown features highlighted context protective antibody responses reactogenicity
Язык: Английский
Процитировано
352
Science, Год журнала: 2021, Номер 374(6573), С. 1353 - 1360
Опубликована: Окт. 26, 2021
Delta’s spike Understanding the molecular mechanisms of increased transmissibility and immune evasion severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is critical to guiding current future intervention strategies. Zhang et al . determined cryo–electron microscopy structures full-length protein trimers Delta, Kappa, Gamma SARS-CoV-2 studied their function antigenic properties. The Delta fused membranes more efficiently at low levels cellular receptor ACE2, its pseudotyped viruses infected target cells substantially rapidly than all other tested, possibly least partly accounting for heightened transmissibility. Mutations each variant rearranged surface N-terminal domain but only caused local changes in receptor-binding domain, consistent with greater resistance neutralizing antibodies. These findings elucidate events that have led these adapt human communities evade host immunity. —VV
Язык: Английский
Процитировано
293
Science, Год журнала: 2022, Номер 375(6584), С. 1048 - 1053
Опубликована: Фев. 8, 2022
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant infective strain. We report structures of spike trimer on its own and in complex with angiotensin-converting enzyme (ACE2) or an anti-Omicron antibody. Most mutations are located surface protein change binding epitopes to many current antibodies. In ACE2-binding site, compensating strengthen receptor domain (RBD) ACE2. Both RBD apo form thermodynamically unstable. An unusual RBD-RBD interaction ACE2-spike supports open conformation further reinforces ACE2 trimer. A broad-spectrum therapeutic antibody, JMB2002, which completed a phase 1 clinical trial, maintains neutralizing activity against Omicron. JMB2002 binds differently from other characterized antibodies inhibits binding.
Язык: Английский
Процитировано
274
Current Opinion in Virology, Год журнала: 2021, Номер 50, С. 173 - 182
Опубликована: Сен. 8, 2021
Язык: Английский
Процитировано
195
Nature, Год журнала: 2022, Номер 604(7906), С. 546 - 552
Опубликована: Фев. 28, 2022
Язык: Английский
Процитировано
190
Molecular Cell, Год журнала: 2022, Номер 82(11), С. 2050 - 2068.e6
Опубликована: Март 25, 2022
Язык: Английский
Процитировано
181
Microbiology and Immunology, Год журнала: 2021, Номер 66(1), С. 15 - 23
Опубликована: Сен. 25, 2021
Spike (S) protein cleavage is a crucial step in coronavirus infection. In this review, process discussed, with particular focus on the novel coronavirus, severe acute respiratory syndrome 2 (SARS-CoV-2). Compared influenza virus and paramyxovirus membrane fusion proteins, activation mechanism of S much more complex. The has two sites (S1/S2 S2'), motif for furin protease at S1/S2 site that results from unique four-amino acid insertion one distinguishing features SARS-CoV-2. viral particle incorporates protein, which already undergone by furin, then undergoes further S2' site, mediated type II transmembrane serine (TMPRSS2), after binding to receptor angiotensin-converting enzyme (ACE2) facilitate plasma membrane. addition, SARS-CoV-2 can enter cell endocytosis be proteolytically activated cathepsin L, although not major mode variants enhanced infectivity have been emerging throughout ongoing pandemic, there close relationship between changes cleavability. All four concern carry D614G mutation, indirectly enhances cleavability furin. P681R mutation delta variant directly increases cleavability, enhancing virulence. Changes significantly impact infectivity, tissue tropism, Understanding these mechanisms critical counteracting pandemic.
Язык: Английский
Процитировано
174
Nature Microbiology, Год журнала: 2022, Номер 7(5), С. 640 - 652
Опубликована: Апрель 28, 2022
Язык: Английский
Процитировано
162