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1.
Cell Discov ; 8(1): 65, 2022 Jul 12.
Article in English | MEDLINE | ID: covidwho-1931380

ABSTRACT

The Omicron variant of SARS-CoV-2 carries multiple unusual mutations, particularly in the receptor-binding domain (RBD) of the spike (S) protein. Moreover, host-adapting mutations, such as residues 493, 498, and 501, were also observed in the Omicron RBD, which indicates that it is necessary to evaluate the interspecies transmission risk of the Omicron variant. Herein, we evaluated the interspecies recognition of the Omicron BA.1 and Delta RBDs by 27 ACE2 orthologs, including humans. We found that Omicron BA.1 expanded its receptor binding spectra to palm-civet, rodents, more bats (least horseshoe bat and greater horseshoe bat) and lesser hedgehog tenrec. Additionally, we determined the cryo-electron microscopy (cryo-EM) structure of the Omicron BA.1 S protein complexed with mouse ACE2 (mACE2) and the crystal structure of Omicron RBD complexed with palm-civet ACE2 (cvACE2). Several key residues for the host range have been identified. These results suggest that surveillance should be enhanced on the Omicron variant for its broader-species receptor binding to prevent spillover and expansion of reservoir hosts for a prolonged pandemic.

2.
Immunity ; 55(8): 1501-1514.e3, 2022 Aug 09.
Article in English | MEDLINE | ID: covidwho-1885835

ABSTRACT

SARS-CoV-2 Omicron variant has presented significant challenges to current antibodies and vaccines. Herein, we systematically compared the efficacy of 50 human monoclonal antibodies (mAbs), covering the seven identified epitope classes of the SARS-CoV-2 RBD, against Omicron sub-variants BA.1, BA.1.1, BA.2, and BA.3. Binding and pseudovirus-based neutralizing assays revealed that 37 of the 50 mAbs lost neutralizing activities, whereas the others displayed variably decreased activities against the four Omicron sub-variants. BA.2 was found to be more sensitive to RBD-5 antibodies than the other sub-variants. Furthermore, a quaternary complex structure of BA.1 RBD with three mAbs showing different neutralizing potencies against Omicron provided a basis for understanding the immune evasion of Omicron sub-variants and revealed the lack of G446S mutation accounting for the sensitivity of BA.2 to RBD-5 mAbs. Our results may guide the application of the available mAbs and facilitate the development of universal therapeutic antibodies and vaccines against COVID-19.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Antibodies, Monoclonal , Antibodies, Viral , COVID-19 Vaccines , Humans , Membrane Glycoproteins , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Viral Envelope Proteins
3.
Comput Math Methods Med ; 2022: 3722703, 2022.
Article in English | MEDLINE | ID: covidwho-1765182

ABSTRACT

Objective: To investigate the clinical efficacy of digital subtraction angiography- (DSA-) guided bronchial arterial chemoembolization (BACE) in patients with primary bronchial lung cancer. Methods: A total of 178 patients with primary intermediate and advanced bronchial lung cancer admitted to our hospital from February 2019 to March 2020 were selected as the subjects, and they were divided into control group (84 cases) and observation group (94 cases) according to the different chemotherapy regimens adopted by the patients. The control group was treated with traditional perfusion chemotherapy, and the observation group was treated with DSA-guided BACE interventional therapy, treated for 4 cycles, and followed up until the end of June 2021. The short-term clinical efficacy, hemoptysis remission, and incidence of adverse reactions were compared between the two groups. The mortality and recurrence rates between the two groups from treatment to the end of follow-up were counted, and the quality of life after treatment and 1 year after treatment were compared. Results: The short-term remission rate (73.40% vs. 58.33%), disease control rate (93.62% vs. 84.52%), hemoptysis remission rate (75.00% vs. 41.51%), the quality of life after chemotherapy cycle (90.86 ± 2.55 vs. 78.04 ± 2.21), and the quality of life after 1 year of follow-up (85.68 ± 2.23 vs. 70.27 ± 1.72) in the observation group were significantly higher than those in the control group, and the difference was statistically significant (P < 0.05). The incidence of adverse reactions (9.57% vs. 20.24%), mortality (10.64% vs. 21.43%), and recurrence rate (11.70% vs. 27.38%) during the follow-up period in the observation group were significantly lower than those in control group, and the differences were statistically significant (P < 0.05). Conclusion: DSA-guided BACE interventional therapy for patients with primary middle-advanced bronchial lung cancer has significant efficacy, which can not only reduce the mortality and recurrence rate of patients but also improve the quality of life of patients, with fewer adverse reactions and high safety, which is worthy of promotion.


Subject(s)
Lung Neoplasms , Quality of Life , Bronchi , Humans , Lung , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/therapy , Treatment Outcome
5.
EMBO J ; 40(16): e107786, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-1239217

ABSTRACT

Pangolins have been suggested as potential reservoir of zoonotic viruses, including SARS-CoV-2 causing the global COVID-19 outbreak. Here, we study the binding of two SARS-CoV-2-like viruses isolated from pangolins, GX/P2V/2017 and GD/1/2019, to human angiotensin-converting enzyme 2 (hACE2), the receptor of SARS-CoV-2. We find that the spike protein receptor-binding domain (RBD) of pangolin CoVs binds to hACE2 as efficiently as the SARS-CoV-2 RBD in vitro. Furthermore, incorporation of pangolin CoV RBDs allows entry of pseudotyped VSV particles into hACE2-expressing cells. A screen for binding of pangolin CoV RBDs to ACE2 orthologs from various species suggests a broader host range than that of SARS-CoV-2. Additionally, cryo-EM structures of GX/P2V/2017 and GD/1/2019 RBDs in complex with hACE2 show their molecular binding in modes similar to SARS-CoV-2 RBD. Introducing the Q498H substitution found in pangolin CoVs into the SARS-CoV-2 RBD expands its binding capacity to ACE2 homologs of mouse, rat, and European hedgehog. These findings suggest that these two pangolin CoVs may infect humans, highlighting the necessity of further surveillance of pangolin CoVs.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Betacoronavirus/physiology , Pangolins/virology , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Amino Acid Substitution , Angiotensin-Converting Enzyme 2/chemistry , Animals , Binding Sites , HEK293 Cells , Hedgehogs/virology , Host Specificity , Humans , Mice , Models, Molecular , Phylogeny , Protein Binding , Protein Conformation , Rats , Spike Glycoprotein, Coronavirus/genetics , Virus Internalization
6.
Geophys Res Lett ; 48(4): 2e020GL091265, 2021 Feb 28.
Article in English | MEDLINE | ID: covidwho-1104432

ABSTRACT

Satellite HCHO data are widely used as a reliable proxy of non-methane volatile organic compounds (NMVOCs) to constrain underlying emissions and chemistry. Here, we examine global significant changes in HCHO columns at the early stage of the COVID-19 pandemic (January-April 2020) compared with the same period in 2019 with observations from the TROPOspheric Monitoring Instrument (TROPOMI). HCHO columns decline (11.0%) in the Northern China Plain (NCP) because of a combination of meteorological impacts, lower HCHO yields as NO x emission plunges (by 36.0%), and reduced NMVOC emissions (by 15.0%) resulting from the lockdown. HCHO columns change near Beijing (+8.4%) due mainly to elevated hydroxyl radical as NO x emission decreases in a NO x -saturated regime. HCHO columns change in Australia (+17.5%), Northeastern Myanmar of Southeast Asia (+14.9%), Central Africa (+7.8%), and Central America (+18.9%), consistent with fire activities. Our work also points to other changes related to temperature and meteorological variations.

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