ABSTRACT
In the face of the COVID-19 pandemic, there is still a lack of miracle drugs for treatment. Repurposing drugs such as Remdesivir and corticosteroids to treat COVID-19 are being studied. Traditional Chinese medicine was widely used during the outbreak of Severe Acute Respiratory Syndrome (SARS) coronavirus infection in China in 2003. It was found that standard medical treatment combined with Chinese medicine treatment may improve the symptoms of SARS patients and speeding resolution of lung infiltration. The commonly used prescriptions for preventing the coronavirus infection are Sangjuyin plus Yupingfeng powder. Various Traditional Chinese medicines with potential to fight SARS-CoV-2 include Liquorice Root and Rhizome, Rhubarb, Heartleaf Houttuynia Herb, Indi-gowoad Root, Tangerine Peel, Scutellaria Root, and Red Sage Root and Rhizome etc. In addition, Chinese patent medicines including Shuanghuanglian Oral liquid, Lianhua Qingwen Capsule, Jinhua Qinggan Granule and Taiwan Chingguan Yihau are recognized as plausible agents for the treatment of novel coronavirus pneumonia. The antiviral, anti-inflammatory and immunomodulatory effects of selected Chinese herbal drugs may attribute to their inhibiting the binding of the coronavirus spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor, inhibiting key enzymes such as 3-chymotrypsin-like protease and ribonucleic acid (RNA)- dependent RNA polymerase during viral replication, and reducing pro-inflammatory cytokines. Since most of the relevant studies mentioned the potential anti-SARS-CoV-2 activity of these agents were only in vitro and animal experiments, more randomized double-blind controlled trials are needed to provide reliable evidence of clinical efficacy in future.
ABSTRACT
The introduction of vaccines has inspired hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against SARS-CoV-2, thus we profiled the earliest humoral signatures in a large cohort of acutely ill (survivors and nonsurvivors) and mild or asymptomatic individuals with COVID-19. Although a SARS-CoV-2-specific immune response evolved rapidly in survivors of COVID-19, nonsurvivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibodies. Given the conservation of S2 across 0-coronaviruses, we found that the early development of SARS-CoV-2-specific immunity occurred in tandem with preexisting common I3-coronavirus OC43 humoral immunity in survivors, which was also selectively expanded in individuals that develop a paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.
ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic has led to accelerated efforts to develop therapeutics and vaccines. A key target of these efforts is the spike (S) protein, which is metastable and difficult to produce recombinantly. We characterized 100 structure-guided spike designs and identified 26 individual substitutions that increased protein yields and stability. Testing combinations of beneficial substitutions resulted in the identification of HexaPro, a variant with six beneficial proline substitutions exhibiting higher expression than its parental construct (by a factor of 10) as well as the ability to withstand heat stress, storage at room temperature, and three freeze-thaw cycles. A cryo-electron microscopy structure of HexaPro at a resolution of 3.2 angstroms confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).