Characteristics of SARS - CoV - 2 nucleic acids and serum antibodies in different clinical specimens and their correlation with the course of COVID -19

To investigate the characteristics of the nucleic acids of severe acute respiratory syndrome coronavirus (SARS-CoV) -2 and antibodies in different specimens obtained from coronavirus disease 2019 (COVID-19) patients;if a correlation between these parameters and the disease course was present. The throat swabs and stool samples of 39 COVID-19 patients admitted to our hospital were collected in this study. Real-time reverse transcription-quantitative polymerase chain reaction (RT-PCR) was undertaken on throat swabs and stool samples. Peripheral blood was taken and serum levels of immunoglobulin IgM and IgG measured. Results showed That, Throat swabs and stool samples tested positive for the nucleic acid of SARS-CoV-Z, but nucleic acid levels were reduced significantly 15 days after disease onset compared with that upon diagnosis. The Ct value of the nucleic acid test was increased significantly. Serum levels of IgM and IgG were significantly higher than those of healthy people. nucleic acid loads in throat swabs and stool samples as well as serum levels of IgM and IgG were highly correlated with the disease course (r = 0.7387,0.5696, -0.546 and 0.6117,respectively, P < 0.05). In this study nucleic acid loads in throat swabs and stool samples as well as serum levels of IgM and IgG are highly correlated with the course of COVID-19.

Benefit from a high store visiting cost in an omnichannel with BOPS.

Omnichannel sales surge in the coronavirus pandemic. This paper establishes an analytical model to study when a firm can benefit from implementing the omnichannel strategy of buy-online and pick-up in-store (BOPS), where the market characteristics are captured by the two-dimensional heterogeneity of product valuation and online waiting cost. The increase in the store visiting cost will reduce BOPS consumers' willingness to pay, but it will also strengthen the encroachment of BOPS on traditional dual-channel. The results show that the firm can benefit from the BOPS strategy when the store visiting cost is relatively high. This well explains the rapid development of the omnichannel with BOPS because of a high store visiting cost during COVID-19. Furthermore, sharply contrasting to the traditional dual-channel sales in which a higher store visiting cost always hurts the firm, the profit under BOPS can be nonmonotonic in the store visiting cost and the firm can benefit from a higher store visiting cost. Specifically, the combination of cross-selling effect, BOPS encroachment effect and BOPS expansion reduction effect associated with the store visiting cost can result in a U-shaped or inverse U-shaped BOPS profit. In addition, introducing BOPS motivates the firm to either increase or decrease the optimal price, conditional on the store visiting cost. For consumers, online and offline consumers can also indirectly benefit from the BOPS strategy, though they may not enjoy the BOPS service.

Targeted protein degradation: from small molecules to complex organelles-a Keystone Symposia report.

Targeted protein degradation is critical for proper cellular function and development. Protein degradation pathways, such as the ubiquitin proteasomes system, autophagy, and endosome-lysosome pathway, must be tightly regulated to ensure proper elimination of misfolded and aggregated proteins and regulate changing protein levels during cellular differentiation, while ensuring that normal proteins remain unscathed. Protein degradation pathways have also garnered interest as a means to selectively eliminate target proteins that may be difficult to inhibit via other mechanisms. On June 7 and 8, 2021, several experts in protein degradation pathways met virtually for the Keystone eSymposium "Targeting protein degradation: from small molecules to complex organelles." The event brought together researchers working in different protein degradation pathways in an effort to begin to develop a holistic, integrated vision of protein degradation that incorporates all the major pathways to understand how changes in them can lead to disease pathology and, alternatively, how they can be leveraged for novel therapeutics.

Impact of Self-Perceived Employability on Sustainable Career Development in Times of COVID-19: Two Mediating Paths

The outbreak of COVID-19 added further stress to individuals' work life, and employability may be especially important to help individuals to pursue sustainable career success in such a context. However, previous studies that examined the impact and the mechanisms of employability on sustainable career success are lacking, especially in the context of pandemic threat. Based on conservation of resource theory (COR), the current study aims to explore whether and how employability, as an important resource, reduced work-related emotional exhaustion and increased work engagement during the COVID-19 pandemic. We expected that self-perceived employability would reduce emotional exhaustion and increase work engagement. We further expected that coping strategy mediated the effect of self-perceived employability on emotional exhaustion, and career commitment mediated its effect on work engagement. Data were collected via a national survey in China among a sample of 4990 human resource practitioners from October to December 2020 amid the COVID-19 outbreak. The proposed model was tested with structural equation modelling. Results supported the proposed model. Self-perceived employability reduced emotional exhaustion and to a larger extent, increases work engagement. The two mediating effects were of partial mediation. The implications of the results for theory and practice are discussed.

Discovery and Nanosized Preparations of (S,R)-Tylophorine Malate as Novel anti-SARS-CoV-2 Agents.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has stimulated the search for effective drugs for its prevention and treatment. Natural products are an important source for new drug discovery. Here, we report that, NK007(S,R), a tylophorine malate, displays high antiviral activity against SARS-CoV-2 with an EC50 0.03 µM in vitro, which is substantially lower than that of remdesivir (EC50: 0.8 µM in vitro), the only authorized drug to date. The histopathological research revealed that NK007(S,R) (5 mg/kg/dose) displayed a protection effect in lung injury induced by SARS-CoV-2, which is better than remdesivir (25 mg/kg/dose). We also prepared two nanosized preparations of NK007(S,R), which also showed good efficacy (EC50: NP-NK007, 0.007 µM in vitro; LP-NK007, 0.014 µM in vitro). Our findings suggest that tylophora alkaloids, isolated from the traditional Chinese medicine Cynanchum komarovii AL, offer a new skeleton for the development of anticoronavirus drug candidate.

A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants.

The successive emergences and accelerating spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and evolved resistance to some ongoing clinical therapeutics increase the risks associated with the coronavirus disease 2019 (COVID-19) pandemic. An urgent intervention for broadly effective therapies to limit the morbidity and mortality of COVID-19 and future transmission events from SARS-related coronaviruses (SARSr-CoVs) is needed. Here, we isolate and humanize an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), named h11B11, which exhibits potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages. When administered therapeutically or prophylactically in the hACE2 mouse model, h11B11 alleviates and prevents SARS-CoV-2 replication and virus-induced pathological syndromes. No significant changes in blood pressure and hematology chemistry toxicology were observed after injections of multiple high dosages of h11B11 in cynomolgus monkeys. Analysis of the structures of the h11B11/ACE2 and receptor-binding domain (RBD)/ACE2 complexes shows hindrance and epitope competition of the MAb and RBD for the receptor. Together, these results suggest h11B11 as a potential therapeutic countermeasure against SARS-CoV, SARS-CoV-2, and escape variants.

The homology analysis of ACE2 gene and its distinct expression in laboratory and wild animals (preprint)

Angiotensin-converting enzyme-2 (ACE2) has been recognized as an entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cells while bats has been suspected as natural host of SARS-CoV-2. However, the detail of intermediate host or the route of transmission of SARS-CoV-2 is still unclear. In this study, we analyze the conservation of ACE2 gene in 11 laboratory and wild animals that live in close proximity either with Bats or human and further investigated its RNA and protein expression pattern in wild bats, mice and tree shrew. We verified that the wild-bats and mice were belonged to Hipposideros pomona and Rattus norvegicus, respectively. ACE2 gene is highly conserved among all 11 animals species at the DNA level. Phylogenetic analysis based on the ACE2 nucleotide sequences revealed that wild bat and Tree shrew were forming a cluster close to human. We further report that ACE2 RNA expression pattern is highly species-specific in different tissues of different animals. Most notably, we found that the expression pattern of ACE2 RNA and protein are very different in each animal species. In summary, our results suggested that ACE2 gene is highly conserved among all 11 animals species. However, different relative expression pattern of ACE2 RNA and protein in each animal species is interesting. Further research is needed to clarify the possible connection between different relative expression pattern of ACE2 RNA and protein in different laboratory and wild animal species and the susceptibility to SARS-CoV-2 infection.

An in-silico approach to identify the potential hot spots in SARS-CoV-2 spike RBD to block the interaction with ACE2 receptor.

A novel acute viral pneumonia induced by SARS-CoV-2 exploded at the end of 2019, causing a severe medical and economic crisis. For developing specific pharmacotherapy against SARS-CoV-2, an in silico virtual screening was developed for the available in-house molecules. The conserved domain analysis was performed to identify the highly conserved and exposed amino acid regions in the SARS-CoV-2-S RBD sites. The Protein-Protein interaction analyses demonstrated the higher affinity between the SARS-CoV-2-S and ACE2 due to varieties of significant interactions between them. The computational alanine scanning mutation study has recognized the highly stabilized amino acids in the SARS-CoV-2-S RBD/ACE2 complex. The cumulative sequence investigations have inferred that Lys417, Phe486, Asn487, Tyr489, and Gln493 are perhaps the iconic target amino acids to develop a drug molecule or vaccine against SARS-CoV-2 infection. Most of the selected compounds include luteolin, zhebeirine, 3-dehydroverticine, embelin, andrographolide, ophiopogonin D, crocin-1, sprengerinin A, B, C, peimine, etc. were exhibited distinguish drug actions through the strong hydrogen bonding with the hot spots of the RBD. Besides, the 100 ns molecular dynamics simulation and free energy binding analysis showed the significant efficacy of luteolin to inhibit the infection of SARS-CoV-2. Highlights:Highly conserved and exposed amino acids in the SARS-CoV-2-S-RBD sites has been identifiedComputational alanine scanning mutation study has recognized the highly stabilized hot spots in the SARS-CoV-2-S RBD/ACE2 complex.Virtual screening has been executed to identify the drug actions in the RBD regionMost of the selected natural products were involved in the distinctive strong interactions with hot spots of RBD to inhibit the infection of SARS-CoV-2.[Formula: see text] Communicated by Ramaswamy H. Sarma.

Network controllability-based algorithm to target personalized driver genes for discovering combinatorial drugs of individual patients.

Multiple driver genes in individual patient samples may cause resistance to individual drugs in precision medicine. However, current computational methods have not studied how to fill the gap between personalized driver gene identification and combinatorial drug discovery for individual patients. Here, we developed a novel structural network controllability-based personalized driver genes and combinatorial drug identification algorithm (CPGD), aiming to identify combinatorial drugs for an individual patient by targeting personalized driver genes from network controllability perspective. On two benchmark disease datasets (i.e. breast cancer and lung cancer datasets), performance of CPGD is superior to that of other state-of-the-art driver gene-focus methods in terms of discovery rate among prior-known clinical efficacious combinatorial drugs. Especially on breast cancer dataset, CPGD evaluated synergistic effect of pairwise drug combinations by measuring synergistic effect of their corresponding personalized driver gene modules, which are affected by a given targeting personalized driver gene set of drugs. The results showed that CPGD performs better than existing synergistic combinatorial strategies in identifying clinical efficacious paired combinatorial drugs. Furthermore, CPGD enhanced cancer subtyping by computationally providing personalized side effect signatures for individual patients. In addition, CPGD identified 90 drug combinations candidates from SARS-COV2 dataset as potential drug repurposing candidates for recently spreading COVID-19.

Simple Strategy for Rapid and Sensitive Detection of 2019 novel coronavirus Based on Antibody (preprint)

Objectives: Since December 2019, acute respiratory disease due to 2019 novel coronavirus emerged in Wuhan city and rapidly spread throughout China. Real-time RT-PCR is widely deployed in diagnostic virology. However, the positive detection rates of RT-PCR are only 30% to 50%. Therefore, we propose a simple strategy for rapidly and sensitively detecting the IgM/IgG antibody against 2019-nCoV using a colloidal gold-based immunochromatographic strip test.Methods A total of 41 clinically 2019-nCoV suspected cases (23 males and 18 females) were enrolled. The sensitivity of colloidal gold-based immunochromatographic strip test and of RT-PCR were compared and evaluated. McNemar’s test was used to compare the detection rate of both assays (P<0.05).Results: The Antibody was detected in 63.4% (26/41) of blood specimens using the assay. In contrast, the 2019-nCoV was detected in 46.3% (19/41) of nasal and pharyngeal swab specimens using the RT-PCR assays. The detection rate obtained by this assay was markedly higher than that obtained by the RT-PCR assays (P=0.039)Conclusion: This detection assay exhibits a higher detection sensitivity than RT-PCR. More important, the assay shows the benefits of easy operation and setup. We believe that the sensitive and time-saving approach may be used as an auxiliary diagnostic tool for 2019-nCoV detection and virus screening and confirmation.