Development of HBsAg-Binding Aptamers that bind HepG2.2.15 cells via HBV surface antigen

Hepatitis B virus surface antigen （HBsAg）, a specific antigen on the membrane of Hepatitis B virus （HBV）-infected cells, provides a perfect target for therapeutic drugs. The development of reagents with high affinity and specificity to the HBsAg is of great significance to the early-stage diagnosis and treatment of HBV infection. Herein, we report the selection of RNA aptamers that can specifically bind to HBsAg protein and HBsAg-positive hepatocytes. One high affinity aptamer, HBs-A22, was isolated from an initial 115 met library of -1.1 ×10^15 random-sequence RNA molecules using the SELEX procedure. The selected aptamer HBs-A22 bound specifically to hepatoma cell line HepG2.2.15 that expresses HBsAg but did not bind to HBsAg-devoid HepG2 cells. This is the first reported RNA aptamer which could bind to a HBV specific antigen. This newly isolated aptamer could be modified to deliver imaging, diagnostic, and therapeutic agents targeted at HBV-infected cells.

Role of Darunavir/Cobicisitat for treating COVID-19:initial virological and clinical findings

Background:COVID-19 remains a common threat to public health.In this study,we evaluated the antiviral effects and safety of Darunavir/Cobicisitat(DRV/c)in patients with confirmed COVID-19.Patients and Methods:We studied 66 patients with COVID-19 infection who were admitted to Zhongnan Hospital of Wuhan University between February 3 and March 11,2020.The patients were divided into the DRV/c and the control groups.The primary endpoint was the time of SARS-CoV-2 nucleic acid conversion detected in respiratory specimens.Results:Subjects with confirmed SARS-CoV-2 infection(n=66)were enrolled in this study;32 subjects were enrolled in the DRV/c group and 34 in the control group.The mean time to nucleic acid conversion(NAC)was shorter in the DRV/c group.The cumulative nucleic acid conversion rate(CNACR)in the DRV/c group was higher during the first two weeks,but the difference was not statistically significant.The proportion of fever during hospitalization in the DRV/c group was significantly lower than in the control group(P-value=0.01).It was found that,in the DRV/c group,the NAC of patients with a duration from symptom onset to admission within three days was significantly shorter(7.9±6.7 days)than in patients with a duration from symptom onset to admission above three days(15.9±7.1 days)(P=0.01).Conclusion:Although the combination of DRV/c and routine treatment for patients with non-severe COVID-19 can significantly reduce the proportion of fever after admission,no significant differences were observed between the DRV/c group and the conventional therapy group,including the overall time to NAC,safety,and tolerability.

Clinical characteristics of four cancer patients with SARS-CoV-2 infection in Wuhan, China

Background The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)led to the outbreak of pneumonia in Wuhan.The virus is highly infectious.Patients with cancer might be susceptible to the viral infection because of the immunosuppressive state cause by therapies on tumors.Case presentation We present the clinical features of four cancer patients who were infected with SARS-CoV-2 in late January of 2020 in our hospital.Cases 1 and 3 were diagnosed as mild and common type of coronavirus disease 2019(COVID-2019)and survived from the viral infection.They acquired SARS-CoV-2 infection during their staying in hospital under radiotherapy and surgery of the tumors.Cases 2 and 4 suffered from severe type of COVID-19,and Case 2 was dead owning to the advanced age,uncontrolled chronic B cell lymphocytic leukemia and many other underlying diseases.The immunosuppressive state induced by liver transplantation and anti-rejection therapy might contribute to the severity of COVID-19 in Case 4,who suffered from hepatitis B related hepatocellular carcinoma.However,Case 4 was recovered from COVID-19 after a combination therapy against virus,bacteria and fungi,and also respiratory support.Nearly all patients showed a decrease in lymphocytes including total CD3+T cells,B cells,and natural killer cells after infection of the virus.Conclusions The severity of COVID-19 might be influenced by immune system state and underlying diseases in cancer patients.And the treatment of SARS-CoV-2 infection in cancer patients is challenged by the immunosuppressive state of these patients under chemotherapy or surgery.