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With the outbreak and pandemic of coronavirus disease-2019 (COVID-19), a huge number of people died of it. Apart from lung injuries, multiple organs have been confirmed to be impaired. In COVID-19 time, primary wound healing processes always prolong, however, its possible underlying mechanisms are still unclear. Therefore, to overcome this clinical problem, clarifying its underlying mechanisms clearly is necessary and urgently needed. In this review, we summarized that COVID-19 can prolong primary wound healing by inducing excessive inflammation and oxidative stress, disturbing immune system and haematological system, as well as influencing the functions and viability of epidermal stem cells (ESCs). Otherwise, we summarized that the strict control measures of blocking up COVID-19 pandemic can also have side effects on primary wound healing process., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

The COVID-19 outbreak brought online learning to the forefront of education. Scholars have conducted many studies on online learning during the pandemic, but only a few have performed quantitative comparative analyses of students' online learning behavior before and after the outbreak. We collected review data from China's massive open online course platform called icourse.163 and performed social network analysis on 15 courses to explore courses' interaction characteristics before, during, and after the COVID-19 pan-demic. Specifically, we focused on the following aspects: (1) variations in the scale of online learning amid COVID-19; (2a) the characteristics of online learning interaction during the pandemic; (2b) the characteristics of online learning interaction after the pandemic; and (3) differences in the interaction characteristics of social science courses and natural science courses. Results revealed that only a small number of courses witnessed an uptick in online interaction, suggesting that the pandemic's role in promoting the scale of courses was not significant. During the pandemic, online learning interaction became more frequent among course network members whose interaction scale increased. After the pandemic, although the scale of interaction declined, online learning interaction became more effective. The scale and level of interaction in Electrodynamics (a natural science course) and Economics (a social science course) both rose during the pan-demic. However, long after the pandemic, the Economics course sustained online interaction whereas interaction in the Electrodynamics course steadily declined. This discrepancy could be due to the unique characteristics of natural science courses and social science courses., Competing Interests: The authors have declared that no competing interests exist.

Background: Previous studies showed that recovered coronavirus disease 2019 (COVID-19) patients can have a subsequent positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after they are discharged from the hospital. Understanding the epidemiological characteristics of recovered COVID-19 patients who have a re-positive test is vital for preventing a second wave of COVID-19., Methods: This retrospective study analyzed the epidemiological and clinical features of 20,280 COVID-19 patients from multiple centers in Wuhan who had a positive PCR test between December 31, 2019, and August 4, 2020. The RT-PCR test results for 4079 individuals who had close contact with the re-positive cases were also obtained., Results: In total, 2466 (12.16%) of the 20,280 patients had a re-positive SARS-CoV-2 PCR test after they were discharged from the hospital, and 4079 individuals had close contact with members of this patient group. All of these 4079 individuals had a negative SARS-CoV-2 PCR test., Conclusions: This retrospective study in Wuhan analyzed the basic characteristics of recovered COVID-19 patients with re-positive PCR test and found that these cases may not be infectious.

Aims & Objective: Coronavirus Disease 2019 (COVID-19) caused by the human coronavirus 2019 (HCoV-19, also known as SARS-CoV-2) infection is currently in a global outbreak. COVID-19 has posed a huge threat to public health and economic stability worldwide. CR3022, a human monoclonal neutralizing antibody isolated from a Severe Acute Respiratory Syndrome (SARS) recovery patient, was confirmed to be able to bind the S protein of HCoV-19 with a certain degree of neutralizing activity. Crystal structural information indicated that CR3022 could bind to the epitope on the receptor binding domain (RBD) of HCoV-19, whose epitope consists of 28 amino acids, and 24 of them are conserved in SARS-CoV of SARS. However, the crystal structure is only a static conformation at a certain moment in time, and it cannot provide dynamic details of the interaction between antigen and antibody., Methods: In this study, molecular dynamics (MD) simulation combined with MM/PBSA and CAS methods were performed to investigate the mechanism of binding of CR3022 against SARS-CoVRBD and HCoV-19-RBD in order to determine their holographic dynamic information., Results: It was found that the CR3022-SARS-CoV-RBD complex was more stable during 100ns MD run than that of the CR3022-HCoV-19-RBD system. There were common conservative amino acids on the β2 sheet of RBD, including Tyr369, Phe377, Lys378, Tyr380, Gly381, Lys386, Leu390 and others. These conservative amino acids play significant roles in the binding process of CR3022 antibody against SARS-CoV-RBD and HCoV-19-RBD. It was also found that the binding mode of CR3022 to its native target SARS-CoV-RBD is more comprehensive and uniform. Moreover, the β2 sheet residue Thr385 and non-β2 sheet residues Arg408 and Asp428 of the CR3022-SARS-CoV-RBD system were found to be crucial for their binding affinities, thus forming a special conformational epitope. However, these key amino acids are not present in the CR3022-HCoV-19-RBD system. The binding mode of CR3022 and HCoV-19-RBD is similar to that of SARS-CoV-RBD, but the deficiency of crucial hydrogen-bonds and salt-bridges. Therefore, the binding of CR3022 and HCoV-19-RBD only draws on the partial mode of the binding of CR3022 and SARS-CoV-RBD, so there is a loss of affinity., Conclusion: Thus, in order to better fight the epidemic of COVID-19 with the CR3022 antibody, this antibody needs to further improve the neutralization efficiency of HCoV-19 through mutation of it's CDR region., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Acute lung injury (ALI), a devastating illness induced by systemic inflammation e.g., sepsis or local lung inflammation e.g., COVID-19 mediated severe pneumonia, has an unacceptably high mortality and has no effective therapy. ALI is associated with increased pulmonary microvascular hyperpermeability and alveolar flooding. The small Rho GTPases, RhoA and Rac1 are central regulators of vascular permeability through cytoskeleton rearrangements. RhoA and Rac1 have opposing functional outcome: RhoA induces an endothelial contractile phenotype and barrier disruption, while Rac1 stabilizes endothelial junctions and increases barrier integrity. In ALI, RhoA activity is increased while Rac1 activity is reduced. We have shown that the activation of RhoA in lipopolysaccharide (LPS)-mediated ALI, is dependent, at least in part, on a single nitration event at tyrosine (Y) 34 . Thus, the purpose of this study was to determine if the inhibition of Rac1 is also dependent on its nitration. Our data show that Rac1 inhibition by LPS is associated with its nitration that mass spectrometry identified as Y 32 , within the switch I region adjacent to the nucleotide-binding site. Using a molecular modeling approach, we designed a nitration shielding peptide for Rac1, designated NipR2 (nitration inhibitor peptide for the Rho GTPases 2), which attenuated the LPS-induced nitration of Rac1 at Y 32 , preserves Rac1 activity and attenuates the LPS-mediated disruption of the endothelial barrier in human lung microvascular endothelial cells (HLMVEC). Using a murine model of ALI induced by intratracheal installation of LPS we found that NipR2 successfully prevented Rac1 nitration and Rac1 inhibition, and more importantly attenuated pulmonary inflammation, reduced lung injury and prevented the loss of lung function. Together, our data identify a new post-translational mechanism of Rac1 inhibition through its nitration at Y 32 . As NipR2 also reduces sepsis induced ALI in the mouse lung, we conclude that Rac1 nitration is a therapeutic target in ALI., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The COVID-19 epidemic is raging around the world. Neutralizing antibodies are powerful tools for the prevention and treatment of SARS-CoV-2 infection. Antibody CR3022, a SARS-CoV neutralizing antibody, was found to cross-react with SARS-CoV-2, but its affinity was lower than that of its binding with SARS-CoV, which greatly limited the further development of CR3022 against SARS-CoV-2. Therefore, it is necessary to improve its affinity to SARS-CoV-2 in vitro. In this study, the structure-based molecular simulations were utilized to virtually mutate the possible key residues in the complementarity-determining regions (CDRs) of the CR3022 antibody. According to the criteria of mutation energy, the mutation sites that have the potential to impact the antibody affinity were then selected. Then optimized CR3022 mutants with the enhanced affinity were further identified and verified by enzyme-linked immunosorbent assay (ELISA), surface plasma resonance (SPR) and autoimmune reactivity experiments. Finally, molecular dynamics (MD) simulation and binding free energy calculation (MM/PBSA) were performed on the wild-type CR3022 and its two double-site mutants to understand in more detail the contribution of these sites to the higher affinity. It was found that the binding affinity of the CR3022 antibody could be significantly enhanced more than ten times after the introduction of the S103F/Y mutation in HCDR–3 and the S33R mutation in LCDR–1. The additional hydrogen-bonding, hydrophobic interactions, as well as salt-bridges formed between the modified double-site mutated antibody and SARS-CoV-2 RBD were identified. The computational and experimental results clearly demonstrated that the affinity of the modified antibody has been greatly enhanced. This study indicates that CR3022 as a neutralizing antibody recognizing the conserved region of RBD against SARS-CoV with cross-reactivity with SARS-CoV-2, a different member in a large family of coronaviruses, could be improved by the computational and experimental approaches which provided insights for developing antibody drugs against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is highly homologous to SARS-CoV. To date, the main protease (Mpro) of SARS-CoV-2 is regarded as an important drug target for the treatment of Coronavirus Disease 2019 (COVID-19). Some experiments confirmed that several HIV protease inhibitors present the inhibitory effects on the replication of SARS-CoV-2 by inhibiting Mpro. However, the mechanism of action has still not been studied very clearly. In this work, the interaction mechanism of four HIV protease inhibitors Darunavir (DRV), Lopinavir (LPV), Nelfinavir (NFV), and Ritonavire (RTV) targeting SARS-CoV-2 Mpro was explored by applying docking, molecular dynamics (MD) simulations, and MM–GBSA methods using the broad-spectrum antiviral drug Ribavirin (RBV) as the negative and nonspecific control. Our results revealed that LPV, RTV, and NFV have higher binding affinities with Mpro, and they all interact with catalytic residues His41 and the other two key amino acids Met49 and Met165. Pharmacophore model analysis further revealed that the aromatic ring, hydrogen bond donor, and hydrophobic group are the essential infrastructure of Mpro inhibitors. Overall, this study applied computational simulation methods to study the interaction mechanism of HIV-1 protease inhibitors with SARS-CoV-2 Mpro, and the findings provide useful insights for the development of novel anti-SARS-CoV-2 agents for the treatment of COVID-19. [ABSTRACT FROM AUTHOR]