Highly conserved binding region of ACE2 as a receptor for SARS-CoV-2 between humans and mammals.

Several cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection transmitted from human owners to their dogs have recently been reported. The first ever case of SARS-CoV-2 transmission from a human owner to a domestic cat was confirmed on March 27, 2020. A tiger from a zoo in New York, USA, was also reportedly infected with SARS-CoV-2. It is believed that SARS-CoV-2 was transmitted to tigers from their caretakers, who were previously infected with this virus. On May 25, 2020, the Dutch Minister of Agriculture, Nature and Food Quality reported that two employees were infected with SARS-CoV-2 transmitted from minks. These reports have influenced us to perform a comparative analysis among angiotensin-converting enzyme 2 (ACE2) homologous proteins for verifying the conservation of specific protein regions. One of the most conserved peptides is represented by the peptide "353-KGDFR-357 (H. sapiens ACE2 residue numbering), which is located on the surface of the ACE2 molecule and participates in the binding of SARS-CoV-2 spike receptor binding domain (RBD). Multiple sequence alignments of the ACE2 proteins by ClustalW, whereas the three-dimensional structure of its binding region for the spike glycoprotein of SARS-CoV-2 was assessed by means of Spanner, a structural homology modeling pipeline method. In addition, evolutionary phylogenetic tree analysis by ETE3 was used. ACE2 works as a receptor for the SARS-CoV-2 spike glycoprotein between humans, dogs, cats, tigers, minks, and other animals, except for snakes. The three-dimensional structure of the KGDFR hosting protein region involved in direct interactions with SARS-CoV-2 spike RBD of the mink ACE2 appears to form a loop structurally related to the human ACE2 corresponding protein loop, despite of the reduced available protein length (401 residues of the mink ACE2 available sequence vs 805 residues of the human ACE2). The multiple sequence alignments of the ACE2 proteins shows high homology and complete conservation of the five amino acid residues: 353-KGDFR-357 with humans, dogs, cats, tigers, minks, and other animals, except for snakes. Where the information revealed from our examinations can support precision vaccine design and the discovery of antiviral therapeutics, which will accelerate the development of medical countermeasures, the World Health Organization recently reported on the possible risks of reciprocal infections regarding SARS-CoV-2 transmission from animals to humans.

Effect by mRNA based COVID-19 vaccination on efficiency of therapy with anti-PD-1 blockade

Immune checkpoint inhibitors are drugs that keep the immune system strong enough to attack cancer cells. To date, cancer immunotherapy using immune checkpoint inhibitors has been shown to be effective against various types of cancer. During the coronavirus infectious disease-2019 (COVID-19) pandemic, concern is raised whether clinical treatment with immune checkpoint inhibitors can interfere with COVID-19 vaccination in patients with several malignancies. Recent report shows significantly improved anti-tumor efficacy of the combination of anti-programmed cell death protein-1 (anti-PD-1) therapy and chemotherapy in patients with advanced nasopharyngeal cancer (NPC) who received COVID-19 vaccination, however, the incidence of severe immune-related adverse events was similar. However, our results revealed that there is no medical evidence stating that COVID-19 vaccination significantly improved the efficacy of the combination of anti-PD-1 therapy and chemotherapy in patients with advanced NPC. Clinical studies with large cohorts of large numbers of patients are required to clarify the impact of COVID-19 vaccines on the efficacy of cancer immunotherapy with immune checkpoint inhibitors.

Pathological Evidence for Residual SARS-CoV-2 in the Micrometastatic Niche of a Patient with Ovarian Cancer.

In previous clinical studies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer patients has a high risk of aggravation and mortality than in healthy infected individuals. Inoculation with coronavirus disease 2019 (COVID-19) vaccine reduces the risk of SARS-CoV-2 infection and COVID-19 severity. However, vaccination-induced anti-SARS-CoV-2 antibody production is said to be lower in cancer patients than in healthy individuals. In addition, the rationale for why the condition of patients with cancer worsens with COVID-19 is not well understood. Therefore, we examined the infection status of SARS-CoV-2 in the primary tumor and micrometastasis tissues of the patient with cancer and COVID-19. In this study, the expression of angiotensin-converting enzyme 2 (ACE2) was observed, and SARS-CoV-2 particles was detected in ovarian tissue cells in contact with the micrometastatic niche of the patient with high-grade serous ovarian cancer. We believe that the severity of COVID-19 in patients with cancer can be attributed to these pathological features. Therefore, the pathological findings of patients with advanced and recurrent ovarian cancer infected with SARS-CoV-2 may help decrease COVID-19 severity in patients with other cancer types.

Impact of COVID-19 restrictions on the research environment and motivation of researchers in Japan.

The environment surrounding researchers has changed significantly in the face of COVID-19 restrictions. An online self-reported questionnaire was completed by 10,557 participants between June 15 and 19, 2020. The impact on work/research activities and harassments under COVID-19 conditions was higher among researchers (1963) compared to non-researchers (8572). We further examined the effect of COVID-19 restrictions on 300 researchers. Women were significantly more likely to report being harassed than males. The overall "decrease in research motivation" was higher in women. The restrictions on research activities because of COVID-19 restrictions caused future anxiety and a decrease in research motivation.