ABSTRACT
At present, there are still about 250 million people with chronic hepatitis B virus (HBV) infection around the world, which seriously threatens human life and health. Chronic hepatitis B (CHB) can develop into liver diseases such as liver fibrosis, liver cirrhosis, and hepatocellular carcinoma; however, there is still a limited number of antiviral drugs and an extremely low cure rate in clinical practice, and thus it is urgent to develop new antiviral drugs. HBV has strong hepatotropism and only infects a few primates such as humans and chimpanzees under natural conditions. Whether immune response (innate immunity and adaptive immunity) can effectively recognize and eliminate or inhibit HBV is an important factor leading to different outcomes after virus infection, and cytokines play an important immunoregulatory role in this process. This article summarizes and discusses the research advances in some key cytokines in CHB infection and treatment.
ABSTRACT
The development of broad-spectrum antivirals against human coronaviruses (HCoVs) is critical to combat the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, as well as future outbreaks of emerging CoVs. We have previously identified a polyethylene glycol-conjugated (PEGylated) lipopeptide, EK1C4, with potent pan-CoV fusion inhibitory activity. However, PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo. Therefore, we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment (HR2-CF) of HCoV-OC43. Among these lipopeptides, EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike (S) mutants, as well as other HCoVs and some bat SARS-related coronaviruses (SARSr-CoVs) tested. The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes, better metabolic stability in mouse serum, higher thermostability than the PEGylated lipopeptide EK1C4, suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.
ABSTRACT
Chronic infection of hepatitis B virus(HBV)presents one of the serious public health challenges worldwide.Current treatment of chronic hepatitis B(CHB)is limited,and is composed of interferon and nucleoside/nucleotide reverse transcriptase inhibitors(NRTI).Interferon is poorly tolerated and is only responsive in a small fraction of CHB patients and NRTIs often face the problem of emergence of drug resistance during long-term treatment.The current treatment of CHB earl be improved in several ways including genotyping mutations associated with drug resistance before treatment to guide the choice of NRTIs and suitable combinations among NRTIs and interferon.It is important to continue research in the identification of novel therapeutic targets in the life cycle of HBV or in the host immune system to stimulate the development of new antiviral agents and immunotherapies.Several antivirai agents targeting HBV entry,cecDNA,capsid formation,viral morphogenesis and virion secretion,as well as two therapeutic vaccines are currently being evaluated in preclinical studies or in clinical trials to assess their anti-HBV efficacy.