Reconstitution of the SARS-CoV-2 ribonucleosome provides insights into genomic RNA packaging and regulation by phosphorylation.

The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 is responsible for compaction of the ∼30-kb RNA genome in the ∼90-nm virion. Previous studies suggest that each virion contains 35 to 40 viral ribonucleoprotein (vRNP) complexes, or ribonucleosomes, arrayed along the genome. There is, however, little mechanistic understanding of the vRNP complex. Here, we show that N protein, when combined in vitro with short fragments of the viral genome, forms 15-nm particles similar to the vRNP structures observed within virions. These vRNPs depend on regions of N protein that promote protein-RNA and protein-protein interactions. Phosphorylation of N protein in its disordered serine/arginine region weakens these interactions to generate less compact vRNPs. We propose that unmodified N protein binds structurally diverse regions in genomic RNA to form compact vRNPs within the nucleocapsid, while phosphorylation alters vRNP structure to support other N protein functions in viral transcription.

Reconstitution of the SARS-CoV-2 ribonucleosome provides insights into genomic RNA packaging and regulation by phosphorylation

The nucleocapsid (N) protein of SARS-CoV-2 is responsible for compaction of the ∼30-kb RNA genome in the ∼90-nm virion. Previous studies suggest that each virion contains 35-40 viral ribonucleoprotein (vRNP) complexes, or ribonucleosomes, arrayed along the genome. There is, however, little mechanistic understanding of the vRNP complex. Here, we show that N protein, when combined in vitro with short fragments of the viral genome, forms 15-nm particles similar to the vRNP structures observed within virions. These vRNPs depend on regions of N protein that promote protein-RNA and protein-protein interactions. Phosphorylation of N protein in its disordered serine/arginine (SR) region weakens these interactions to generate less compact vRNPs. We propose that unmodified N protein binds structurally diverse regions in genomic RNA to form compact vRNPs within the nucleocapsid, while phosphorylation alters vRNP structure to support other N protein functions in viral transcription.

An imidazolium-based zwitterionic polymer for antiviral and antibacterial dual functional coatings.

To reduce the severe health risk and the huge economic impact associated with the fomite transmission of SARS-CoV-2, an imidazolium-based zwitterionic polymer was designed, synthesized, and demonstrated to achieve contact deactivation of a human coronavirus under dry ambient conditions that resemble fomite transmission. The zwitterionic polymer further demonstrated excellent antifouling properties, reducing the adhesion of coronavirus and the formation of bacteria biofilms under wetted conditions. The polymer was synthesized using a substrate-independent and solvent-free process, leveraging an all-dry technique named initiated chemical vapor deposition (iCVD). The broad applicability of this approach was demonstrated by applying the polymer to a range of substrates that are curved and/or with high-aspect-ratio nano/microporous structures, which remained intact after the coating process. The zwitterionic polymer and the synthesis approach reported here present an effective solution to mitigate viral transmission without the need for manual disinfection, reducing the health and economic impact of the ongoing pandemic.

Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by binding of the viral Spike protein to host receptor angiotensin-converting enzyme 2 (ACE2), followed by fusion of viral and host membranes. Although antibodies that block this interaction are in emergency use as early coronavirus disease 2019 (COVID-19) therapies, the precise determinants of neutralization potency remain unknown. We discovered a series of antibodies that potently block ACE2 binding but exhibit divergent neutralization efficacy against the live virus. Strikingly, these neutralizing antibodies can inhibit or enhance Spike-mediated membrane fusion and formation of syncytia, which are associated with chronic tissue damage in individuals with COVID-19. As revealed by cryoelectron microscopy, multiple structures of Spike-antibody complexes have distinct binding modes that not only block ACE2 binding but also alter the Spike protein conformational cycle triggered by ACE2 binding. We show that stabilization of different Spike conformations leads to modulation of Spike-mediated membrane fusion with profound implications for COVID-19 pathology and immunity.

Psychological Impact of the COVID-19 Outbreak on Nurses in China: A Nationwide Survey During the Outbreak.

Background: The COVID-19 pandemic is a major public health issue and challenge to health professionals. In similar epidemics, nurses experienced more distress than other providers. Methods: We surveyed both on-duty nurses caring for infected patients and second-line nurses caring for uninfected patients from Hubei and other provinces throughout China. Results: We received completed surveys from 1,364 nurses from 22 provinces: 658 front-line and 706 second-line nurses. The median (IQR) GHQ-28 score of all nurses was 17 (IQR 11-24). The overall incidence of mild-to-moderate distress (GHQ score > 5) was 28%; that for severe distress (GHQ score > 11) was 6%. The incidence of mild-to-moderate distress in the second-line nurses was higher than that in the front-line nurses (31 vs. 25%; OR, 0.74; 95 CI, 0.58-0.94). Living alone (OR, 0.62; 95% CI, 0.44-0.86) and feeling supported (OR, 0.82, 95% CI, 0.74-0.90) independently predicted lower anxiety. Conclusions: During the COVID-19 pandemic, the psychological problems of all nurses were generally serious. The interviewed second-line nurses face more serious issues than the front-line nurses.

Bivalent binding of a fully human IgG to the SARS-CoV-2 spike proteins reveals mechanisms of potent neutralization.

In vitro antibody selection against pathogens from naïve combinatorial libraries can yield various classes of antigen-specific binders that are distinct from those evolved from natural infection 1-4 . Also, rapid neutralizing antibody discovery can be made possible by a strategy that selects for those interfering with pathogen and host interaction 5 . Here we report the discovery of antibodies that neutralize SARS-CoV-2, the virus responsible for the COVID-19 pandemic, from a highly diverse naïve human Fab library. Lead antibody 5A6 blocks the receptor binding domain (RBD) of the viral spike from binding to the host receptor angiotensin converting enzyme 2 (ACE2), neutralizes SARS-CoV-2 infection of Vero E6 cells, and reduces viral replication in reconstituted human nasal and bronchial epithelium models. 5A6 has a high occupancy on the viral surface and exerts its neutralization activity via a bivalent binding mode to the tip of two neighbouring RBDs at the ACE2 interaction interface, one in the "up" and the other in the "down" position, explaining its superior neutralization capacity. Furthermore, 5A6 is insensitive to several spike mutations identified in clinical isolates, including the D614G mutant that has become dominant worldwide. Our results suggest that 5A6 could be an effective prophylactic and therapeutic treatment of COVID-19.

Selection of homemade mask materials for preventing transmission of COVID-19: A laboratory study.

The Coronavirus Disease 2019 (COVID-19) has swept the whole world with high mortality. Since droplet transmission is the main route of transmission, wearing a mask serves as a crucial preventive measure. However, the virus has spread quite quickly, causing severe mask shortage. Finding alternative materials for homemade masks while ensuring the significant performance indicators will help alleviate the shortage of masks. Referring to the national standard for the "Surgical Mask" of China, 17 materials to be selected for homemade masks were tested in four key indicators: pressure difference, particle filtration efficiency, bacterial filtration efficiency and resistance to surface wetting. Eleven single-layer materials met the standard of pressure difference (≤49 Pa), of which 3 met the standard of resistance to surface wetting (≥3), 1 met the standard of particle filtration efficiency (≥30%), but none met the standard of bacterial filtration efficiency (≥95%). Based on the testing results of single-layer materials, fifteen combinations of paired materials were tested. The results showed that three double-layer materials including double-layer medical non-woven fabric, medical non-woven fabric plus non-woven shopping bag, and medical non-woven fabric plus granular tea towel could meet all the standards of pressure difference, particle filtration efficiency, and resistance to surface wetting, and were close to the standard of the bacterial filtration efficiency. In conclusion, if resources are severely lacking and medical masks cannot be obtained, homemade masks using available materials, based on the results of this study, can minimize the chance of infection to the maximum extent.

Antibody-dependent enhancement of coronavirus.

Antibody-dependent enhancement (ADE) exists in several kinds of virus. It has a negative influence on antibody therapy for viral infection. This effect was first identified in dengue virus and has since also been described for coronavirus. To date, the rapid spread of the newly emerged coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has affected over 3.8 million people across the globe. The novel coronavirus poses a great challenge and has caused a wave of panic. In this review, antibody-dependent enhancements in dengue virus and two kinds of coronavirus are summarized. Possible solutions for the effects are reported. We also speculate that ADE may exist in SARS-CoV-2.

Characteristics of the Coronavirus Disease 2019 and related Therapeutic Options.

The coronavirus disease 2019 (COVID-19) is a new type of pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. COVID-19 is affecting millions of patients, and the infected number keeps increasing. SARS-CoV-2 is highly infectious, has a long incubation period, and causes a relatively high death rate, resulting in severe health problems all over the world. Currently there is no effective proven drug for the treatment of COVID-19; therefore, development of effective therapeutic drugs to suppress SARS-CoV-2 infection is urgently needed. In this review, we first summarize the structure and genome features of SARS-CoV-2 and introduce its infection and replication process. Then, we review the clinical symptoms, diagnosis, and treatment options of COVID-19 patients. We further discuss the potential molecular targets and drug development strategies for treatment of the emerging COVID-19. Finally, we summarize clinical trials of some potential therapeutic drugs and the results of vaccine development. This review provides some insights for the treatment of COVID-19.

Effectiveness of N95 respirators versus surgical masks against influenza: A systematic review and meta-analysis.

OBJECTIVE: Previous meta-analyses concluded that there was insufficient evidence to determine the effect of N95 respirators. We aimed to assess the effectiveness of N95 respirators versus surgical masks for prevention of influenza by collecting randomized controlled trials (RCTs). METHODS: We searched PubMed, EMbase and The Cochrane Library from the inception to January 27, 2020 to identify relevant systematic reviews. The RCTs included in systematic reviews were identified. Then we searched the latest published RCTs from the above three databases and searched ClinicalTrials.gov for unpublished RCTs. Two reviewers independently extracted the data and assessed risk of bias. Meta-analyses were conducted to calculate pooled estimates by using RevMan 5.3 software. RESULTS: A total of six RCTs involving 9 171 participants were included. There were no statistically significant differences in preventing laboratory-confirmed influenza (RR = 1.09, 95% CI 0.92-1.28, P > .05), laboratory-confirmed respiratory viral infections (RR = 0.89, 95% CI 0.70-1.11), laboratory-confirmed respiratory infection (RR = 0.74, 95% CI 0.42-1.29) and influenzalike illness (RR = 0.61, 95% CI 0.33-1.14) using N95 respirators and surgical masks. Meta-analysis indicated a protective effect of N95 respirators against laboratory-confirmed bacterial colonization (RR = 0.58, 95% CI 0.43-0.78). CONCLUSION: The use of N95 respirators compared with surgical masks is not associated with a lower risk of laboratory-confirmed influenza. It suggests that N95 respirators should not be recommended for general public and nonhigh-risk medical staff those are not in close contact with influenza patients or suspected patients.