Structural basis of human ACE2 higher binding affinity to currently circulating Omicron SARS-CoV-2 sub-variants BA.2 and BA.1.1.

The currently circulating Omicron sub-variants are the SARS-CoV-2 strains with the highest number of known mutations. Herein, we found that human angiotensin-converting enzyme 2 (hACE2) binding affinity to the receptor-binding domains (RBDs) of the four early Omicron sub-variants (BA.1, BA.1.1, BA.2, and BA.3) follows the order BA.1.1 > BA.2 > BA.3 ≈ BA.1. The complex structures of hACE2 with RBDs of BA.1.1, BA.2, and BA.3 reveal that the higher hACE2 binding affinity of BA.2 than BA.1 is related to the absence of the G496S mutation in BA.2. The R346K mutation in BA.1.1 majorly affects the interaction network in the BA.1.1 RBD/hACE2 interface through long-range alterations and contributes to the higher hACE2 affinity of the BA.1.1 RBD than the BA.1 RBD. These results reveal the structural basis for the distinct hACE2 binding patterns among BA.1.1, BA.2, and BA.3 RBDs.

A review on COVID-19 transmission, epidemiological features, prevention and vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections and millions of deaths over past two years. Currently, many countries have still not been able to take the pandemic under control. In this review, we systematically summarized what we have done to mitigate the COVID-19 pandemic, from the perspectives of virus transmission, public health control measures, to the development and vaccination of COVID-19 vaccines. As a virus most likely coming from bats, the SARS-CoV-2 may transmit among people via airborne, faecal-oral, vertical or foodborne routes. Our meta-analysis suggested that the R0 of COVID-19 was 2.9 (95% CI: 2.7-3.1), and the estimates in Africa and Europe could be higher. The median Rt could decrease by 23-96% following the nonpharmacological interventions, including lockdown, isolation, social distance, and face mask, etc. Comprehensive intervention and lockdown were the most effective measures to control the pandemic. According to the pooled R0 in our meta-analysis, there should be at least 93.3% (95% CI: 89.9-96.2%) people being vaccinated around the world. Limited amount of vaccines and the inequity issues in vaccine allocation call for more international cooperation to achieve the anti-epidemic goals and vaccination fairness.

Molecular insights into receptor binding of recent emerging SARS-CoV-2 variants.

Multiple SARS-CoV-2 variants of concern (VOCs) have been emerging and some have been linked to an increase in case numbers globally. However, there is yet a lack of understanding of the molecular basis for the interactions between the human ACE2 (hACE2) receptor and these VOCs. Here we examined several VOCs including Alpha, Beta, and Gamma, and demonstrate that five variants receptor-binding domain (RBD) increased binding affinity for hACE2, and four variants pseudoviruses increased entry into susceptible cells. Crystal structures of hACE2-RBD complexes help identify the key residues facilitating changes in hACE2 binding affinity. Additionally, soluble hACE2 protein efficiently prevent most of the variants pseudoviruses. Our findings provide important molecular information and may help the development of novel therapeutic and prophylactic agents targeting these emerging mutants.

The molecular basis for SARS-CoV-2 binding to dog ACE2.

SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus.

The impact of COVID-19 pandemic on colorectal cancer patients: a single-center retrospective study.

BACKGROUND: Since December 2019, China has experienced a public health emergency from the coronavirus disease, which has become a pandemic and is impacting the care of cancer patients worldwide. This study evaluated the impact of the pandemic on colorectal cancer (CRC) patients at our center and aimed to share the lessons we learned with clinics currently experiencing this impact. METHODS: We retrospectively collected data on CRC patients admitted between January 1, 2020 and May 3, 2020; the control group comprised patients admitted between January 1, 2019 and May 3, 2019. RESULTS: During the pandemic, outpatient volumes decreased significantly, especially those of nonlocal and elderly patients, whereas the number of patients who received chemotherapy and surgery remained the same. During the pandemic, 710 CRC patients underwent curative resection. The proportion of patients who received laparoscopic surgeries was 49.4%, significantly higher than the 39.5% during the same period in 2019. The proportion of major complication during the pandemic was not significantly different from that of the control group. The mean hospital stay was significantly longer than that of the control group. CONCLUSIONS: CRC patients confirmed to be infection-free can receive routine treatment. Using online medical counseling and appropriate identification, treatment and follow-up can be effectively maintained. Adjuvant and palliative chemotherapy should not be discontinued. Endoscopic polypectomy, elective, palliative, and multidisciplinary surgeries can be postponed, while curative surgery should proceed as usual. For elderly CRC patients, endoscopic surgery and neoadjuvant radiotherapy are recommended.