SARS-CoV-2 has caused the COVID-19 pandemic. Recently, B.1.617 variants have been transmitted rapidly in India. The transmissibility, pathogenicity, and neutralization characteristics of these variants have received considerable interest. In this study, 22 pseudotyped viruses were constructed for B.1.617 variants, as well as 16 corresponding single amino acid mutations. B.1.617 variants did not exhibit enhanced infectivity in humans, but mutations T478K and E484Q in the RBD led to enhanced infectivity in mouse ACE2-overexpressing cells. Furin activities were slightly increased against B.1.617 variants and cell–cell fusion was also enhanced. Furthermore, B.1.617 variants escaped neutralization by several mAbs, mainly because of mutations L452R, T478K, and E484Q in the RBD. The neutralization activities of sera from convalescent patients, inactivated vaccine, or adenovirus vaccine-immunized volunteers; and SARS-CoV-2 immunized animals against pseudotyped B.1.617 variants were reduced by about two-fold compared with the D614G virus.
No higher infectivity but immune escape of SARS-CoV-2 501Y.V2 variants The 501Y.V2 variants of SARS-CoV-2 containing multiple mutations in Spike are now dominant in South Africa and are rapidly spreading to other countries. Here, experiments with 18 pseudotyped viruses showed that the 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed. Notably, the susceptibility of the 501Y.V2 variants to 12 of 17 neutralizing monoclonal antibodies was substantially diminished, and the neutralization ability of the sera from convalescent patients and immunized mice was also reduced for these variants. The neutralization resistance was mainly caused by E484K and N501Y mutations in the receptor-binding domain of Spike. The enhanced infectivity in murine ACE2-overexpressing cells suggests the possibility of spillover of the 501Y.V2 variants to mice. Moreover, the neutralization resistance we detected for the 501Y.V2 variants suggests the potential for compromised efficacy of monoclonal antibodies and vaccines.
Number of positive tests, SGTF dropouts and B117 sequences at Helix from Oct 15, 2020 to Feb 19, 2021. The testing data has been filtered to include only those days with >= 3 tests to protect patient privacy. Inquiries can be made to Helix for additional details if they want to enter into a data transfer agreement.
Publisher: Pontifical Catholic University of Sao Paulo (PUC-SP)
Apresenta-se neste ensaio o conceito de “semiobiônica computacional”, derivado da biônica clássica e que utiliza a semiótica como campo mediador entre o mundo biológico e os sistemas computacionais bioinspirados. O foco é o desenvolvimento de modelos que possam servir à criação de dispositivos de engenharia ou técnicas de simulação em contexto de software. Utilizando-se o ciclo do SARS-CoV-2, apresentado resumidamente, propõe-se um modelo semiobiônico parcial capaz de expressar as relações sígnicas e o fluxo de informação subjacente ao comportamento viral. Dois diagramas são gerados: diagrama semiótico e diagrama do autômato finito análogo ao fenômeno. Ao final, segue reflexão a respeito das possibilidades desta abordagem para o avanço no conhecimento sobre o SARS-CoV-2, bem como para outros agentes biológicos.Palavras-chave: Biônica. Biossemiótica; SARS-CoV-2. Vida artificial.
Publisher: European Open Access Publishing (Europa Publishing)
This computational study comprises of pharmacophore-base virtual screening of the ZINC database, molecular docking of predicted ligands (pharmacophore agent) against the target protein, SARS-CoV-2 (PDB ID: 5r7y) and the prediction of ADMET descriptors using Swiss ADME and PROTOX-II online web servers. Meanwhile, remdesivir, ZINC72392503, ZINC72809903, ZINC06560017, ZINC76101700, ZINC88423098 and ZINC91600695 had a docking scores of -2.0 Kcal/mol, -6.7 Kcal/mol, -6.4 Kcal/mol, -6.0 Kcal/mol, -6.0 Kcal/mol, -6.0 Kcal/mol and-6.0 Kcal/mol respectively. Meanwhile, ZINC72392503 was selected as the lead molecule and was observed to interact with LUE 27, THR 25, CYS 145, THR 26, SER 46, GLY 143, ASN 142, HIS 163, HIS 41, MET 165, GLU 166, ARG 188, GLN 189, HIS 41, MET 49, SER 46 amino acids. The ADME descriptor revealed that the lead molecule was soluble, druggable, void of drug-drug interaction that may inhibit essential enzymatic reaction and was noticed to fall into PROTOX-II toxicity class 3. The lead molecule showed a good affinity for the target protein of SARS-CoV-2, hence, may have a physiological implication that can inhibit a protein responsible for the replication of SARS-CoV-2.