Ubiquitination of SARS-CoV-2 ORF7a Prevents Cell Death Induced by Recruiting BclXL To Activate ER Stress.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has emerged in the last 2 years. The accessory protein ORF7a has been proposed as an immunomodulating factor that can cause dramatic inflammatory responses, but it is unknown how ORF7a interacts with host cells. We show that ORF7a induces cell apoptosis by recruiting the prosurvival factor BclXL to the endoplasmic reticulum (ER) via the exposed C-terminal residues Lys117 and Lys119. Simultaneously, ORF7a activates ER stress via the PERK-elF2α-CHOP pathway and inhibits the expression of endogenous BclXL, resulting in enhanced cell apoptosis. Ubiquitination of ORF7a interrupts the interaction with BclXL in the ER and weakens the activation of ER stress, which to some extent rescues the cells. Our work demonstrates that SARS-CoV-2 ORF7a hires antiapoptosis protein and aggregates on the ER, resulting in ER stress and apoptosis initiation. On the other hand, ORF7a utilizes the ubiquitin system to impede and escape host elimination, providing a promising potential target for developing strategies for minimizing the COVID-19 pandemic. IMPORTANCE Viruses struggle to reproduce after infecting cells, and the host eliminates infected cells through apoptosis to prevent virus spread. Cells adopt a special ubiquitination code to protect against viral infection, while ORF7a manipulates and exploits the ubiquitin system to eliminate host cells' effect on apoptosis and redirect cellular pathways in favor of virus survival. Our results revealed that SARS-CoV-2-encoded accessory protein ORF7a recruits prosurvival factor BclXL to the ER and activates the cellular ER stress response resulting in the initiation of programmed death to remove virus-infected cells. Ubiquitination of ORF7a blocked the recruitment of BclXL and suppressed the ER stress response, which helps to counteract cell apoptosis and rescue cell fate. These findings help us understand the mechanism of SARS-CoV-2 invasion and contribute to a theoretical foundation for the clinical prevention of COVID-19.

Developing Pseudovirus-Based Neutralization Assay against Omicron-Included SARS-CoV-2 Variants

The global spread of SARS-CoV-2 and its variants poses a serious threat to human health worldwide. Recently, the emergence of Omicron has presented a new challenge to the prevention and control of the COVID-19 pandemic. A convenient and reliable in vitro neutralization assay is an important method for validating the efficiency of antibodies, vaccines, and other potential drugs. Here, we established an effective assay based on a pseudovirus carrying a full-length spike (S) protein of SARS-CoV-2 variants in the HIV-1 backbone, with a luciferase reporter gene inserted into the non-replicate pseudovirus genome. The key parameters for packaging the pseudovirus were optimized, including the ratio of the S protein expression plasmids to the HIV backbone plasmids and the collection time for the Alpha, Beta, Gamma, Kappa, and Omicron pseudovirus particles. The pseudovirus neutralization assay was validated using several approved or developed monoclonal antibodies, underscoring that Omicron can escape some neutralizing antibodies, such as REGN10987 and REGN10933, while S309 and ADG-2 still function with reduced neutralization capability. The neutralizing capacity of convalescent plasma from COVID-19 convalescent patients in Wuhan was tested against these pseudoviruses, revealing the immune evasion of Omicron. Our work established a practical pseudovirus-based neutralization assay for SARS-CoV-2 variants, which can be conducted safely under biosafety level-2 (BSL-2) conditions, and this assay will be a promising tool for studying and characterizing vaccines and therapeutic candidates against Omicron-included SARS-CoV-2 variants.

Temporary vaccination clinic for COVID-19 in Zhuhai, China.

Vaccines are urgently needed to control the COVID-19 pandemic. To gradually increase the vaccination rate among residents, temporary vaccination clinic for COVID-19 plays an important role. It should be located in an area with convenient transportation and concentrated population. Functional zones including waiting and inquiry, registration and notification, injection, observation and emergency room should be established. All vaccine recipients' information should be uploaded to the national immunization information system. Medical staff at the temporary vaccination clinic should be professionally trained. A cautious disinfection and wiping are essential for the temporary vaccination clinic.

COVID-19 emergencies around the globe: China's experience in controlling COVID-19 and lessons learned.

MOTIVATION: Nations around the world have been significantly impacted during the COVID-19 pandemic. China's strategies for controlling COVID-19 offer valuable lessons for the global community. By learning from China's experience and lessons, other countries could also find appropriate methods to control the pandemic. PROBLEM STATEMENT: What measures has China taken to control the pandemic? What lessons has China learned through this pandemic? APPROACH/METHODS: The literature on China's lessons and experience in controlling the COVID-19 pandemic was searched and reviewed. Related newspapers and magazines were also searched. RESULTS: China's experience can be summed up as establishing temporary hospitals, strict isolation, experts with a knowledge of COVID-19, and measures that increase social distancing. CONCLUSIONS: By learning from the experience of China, other countries in the world could eventually find the methods to control the COVID-19 pandemic. An emergency response system should be established in each country. Doctors and nurses are not alone in fighting COVID-19, and the entire world is helping them. With cooperation, current difficulties could be overcome.

Complex emergencies of COVID-19: management and experience in Zhuhai, China.

The impact of communicable diseases (infectious diseases) on human health is obvious. The sudden outbreak of COVID-19 (Corona Virus Disease 2019) has made people realise the threat of communicable diseases to mankind. As a city of many migrants, Zhuhai Special Economic Zone experienced great challenges brought about by the COVID-19 epidemic. Experience has been acquired from all aspects of this. A highly reactive, multifunctional and efficient emergency management system should be established, and the significance of information communication should be fully understood for the future.