RIKEN IMS AnnualReport 2020
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64Table: COVID-19-related research conducted at IMSCoV-2 has recently become a pandemic. The sudden emer-gence and spread of SARS-CoV-2 poses a threat to global health and the economy over the world. Although a new vaccine for the SARS-CoV-2 may be available in many countries in the near future, the development of strategies to prevent the virus’s spread is still needed. At present, several groups in IMS are developing tools for COVID-19 diagnosis, prevention and therapy. For the development of diagnostics and biomarkers, Usui’s group already constructed a SARS-CoV-2 detection kit based on the original isothermal amplification technology “SmartAmp method”.  The usefulness of this kit was evaluated with viral genomic RNA of ac-tual SARS-CoV-2 isolated from passengers of the Diamond Prin-cess cruise ship, which was quarantined in Yokohama. The kit was approved by the Pharmaceuticals and Medical Devices Agency in August 2020. Momozawa’s group is working to discover biomark-ers based on the idea that individual differences in immunity-related genes may affect the severity of clinical phenotypes of infection. The identification of such individual differences could reveal the mechanisms of COVID-19 that lead to various clini-cal outcomes. They participate in a global consortium called the COVID Human Genetic Effort and perform whole genome and targeted sequencing in patients. For COVID-19 treatment, many groups are working on SARS-CoV-2 projects. Among them, several groups are collaborating with RIKEN Drug Discovery and Medical Platforms (DMP). Miyauchi’s group previously reported studies of neutralizing an-tibodies against influenza viruses, in which live influenza virus infection induced broad-spectrum neutralizing antibodies in a TFH cell-dependent mechanism. They have applied this knowl-edge to the generation of monoclonal antibodies (mAb) against SARS-CoV-2. So far, they established many hybridoma clones producing anti-CoV-2-S antibody, which were generated from lymph node B cells after co-administration of the SARS-CoV-2-spike (S) protein and live influenza viruses to mice. Saito’s group is working on a different type of neutralizing antibody, one for TMPRSS2. TMPRSS2 is critical for viral entry based on stud-ies showing that small molecule inhibitors of TMPRSS2 inhibit SARS-CoV-2 infection. However, these inhibitors have some side effects and his group thinks that TMPRSS2 mAb may more specifically inhibit the infection. As a Drug Discovery Antibody Platform Unit, they have tried to establish human TMPRSS2 mAb to inhibit SARS-CoV2 infection. Fukuyama’s group already iso-lated several therapeutic human mAbs from COVID-19 patients in collaboration with Keio University. In addition, they showed a vaccine adjuvant effect of vitamin D3 that may lead to a safer COVID-19 vaccine by regulating the vitamin D3 pathway. Fujii’s group previously established the concept of the artificial adjuvant vector cell (aAVC) system against cancer and have now extended it to COVID-19. They established SARS-CoV-2-derived antigen-expressing aAVC (aAVC-Cov-2), and will perform a proof of concept study for anti-viral cytotoxic T cell induction as well as anti-SARS-CoV-2 Ab in vaccinated animals. Recent advances as IMS projects in the fields of diagnostics, treatment and vac-cine development for SARS-CoV-2 infection are summarized in Table.TeamsHidehiro Fukuyama (Lab. for Lymphocyte Differentiation)Yasushi Okazaki (Lab. for Comprehensive Genomic Analysis)Yukihide Momozawa (Lab for Genotyping Development)Hidehiro Fukuyama (Lab. For Lymphocyte Differentiation)Kosuke Miyauchi (Lab. for Cytokine Regulation)Kazuyo Moro (Lab. for Innate Immune Systems)Kenya Honda (Lab. for Gut Homeostasis)Hiroshi Ohno (Lab. for Intestinal Ecosystem)Kengo Usui (Genetic Diagnosis Technology Unit)Takashi Saito (Lab. for Cell Signaling)Shin-Ichiro Fujii (Lab. for Immunotherapy)TitlesDevelopment of COVID-19 antibody drugGenome analysis of SARS-CoV-2Genome analysis to identify genes and genome loci associated with individual differences in susceptibility to COVID-19 infectionIsolation of new coronavirus detection antibody and development of on-site rapid virus detection kitConstruction of a system to isolate a human monoclonal neutralizing antibody against SARS-CoV-2 (with DMP)Development of a new treatment for severe cases of COVID-19Understanding host-gut microbiota interactions to develop a therapeutic/preventive strategy toward SARS-CoV-2 infectionScreening of drug candidate compounds for COVID-19 in large databases using scalable similarity searchesDevelopment of diagnostic methods using SmartAmp technology (with PMI)Development of monoclonal Ab for TMPRSS (with DMP)Development of aAVC-Cov2 (with DMP)COVID-19 projects in IMSCoronavirus disease 2019 (COVID-19) caused by SARS-

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