ABSTRACT
The World Health Organization has declared that the outbreak of coronavirus disease 2019(COVID-19) is a global pandemic. As mutations occurred in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the global epidemic still needs further concern. Worryingly, the effectiveness and neutralizing activity of existing antibodies and vaccines against SARS-CoV-2 variants is declining. There is an urgent need to find an effective antiviral medication with broad-spectrum inhibitory effects on novel coronavirus mutant strains against the SARS-CoV-2 infection. Neutralizing antibodies play an important role in the prevention and treatment of COVID-19. The interaction of spike-receptor-binding domain (Spike-RBD) of SARS-CoV-2 and human angiotensin-converting enzyme 2 (ACE2) is the first and critical step of SARS-CoV-2 infection. Hence, the SARS-CoV-2 Spike-RBD is a hot target for neutralizing antibodies development. Evusheld, the combination of Tixagevimab and Cilgavimab monoclonal antibodies (mAbs) targeting Spike-RBD exhibits neutralizing activity against BA.2.12.1, BA.4 and BA.5, which could be used as pre-exposure prophylaxis against SARS-CoV-2 infection. The nucleocapsid (N) protein is a conservative and high-abundance structural protein of SARS-CoV-2. The nCoV396 monoclonal antibody, isolated from the blood of convalescent COVID-19 patients against the N protein of SARS-CoV-2. This mAb not only showed neutralizing activity but also inhibits hyperactivation of complement and lung injury induced by N protein. The mAb 3E8 targeting ACE2 showed broadly neutralizing activity against SARS-CoV-2 and D614G, B.1.1.7, B.1.351, B.1.617.1 and P.1 variants in vitro and in vivo, but did not impact the biological activity of ACE2. Compared with neutralizing antibodies, small molecule inhibitors have several advantages, such as broad-spectrum inhibitory effect, low cost, and simple administration methods. Several small-molecule inhibitors disrupt viral binding by targeting the ACE2 and N-terminal domain (NTD) of SARS-CoV-2 spike protein. Known drugs such as chloroquine and hydroxychloroquine could also block the infection of SARS-CoV-2 by interacting with residue Lys353 in the peptidase domain of ACE2. The transmembrane protease serine 2 (TMPRSS2) inhibitors Camostat mesylate and Proxalutamide inhibit infection by blocking TMPRSS2 mediates viral membrane fusion. The main protease inhibitor Paxlovid and RNA-dependent RNA polymerase inhibitor Azvudine have been approved for treatment of COVID-19 patients. This review summarizes the current research status of neutralizing antibodies and small molecule inhibitors and prospects for their application. We expect to provide more valuable information for further studies in this field.
ABSTRACT
<p><b>OBJECTIVE</b>To find out an effective therapy for severe child autism.</p><p><b>METHODS</b>Sixty-nine autism children were divided into a JIN's 3-needling group (n=35) and a behavior intervention group (n=34). The JIN's needling group was treated with JIN's 3-needling therapy, including Four-shen needling, Zhi-three needling and Nao-three needling, etc. with point group of the head selected as main points; and the behavior intervention group with professional behavior intervention comprehensive therapy in a special training school for autism children. Childhood autism rating scale (CARS) was used for evaluation of therapeutic effects.</p><p><b>RESULTS</b>After 2 therapeutic courses (240 sessions), the markedly effective rate was 97.1% in the JIN's 3-needling group and 64.7% in the behavior intervention group; there was asignificant difference the therapeutic effect between the two groups (P<0.01); after the first course (first 120 session) and the second course (later 120 sessions), there was a very significant difference between the two groups (P<0.001); and there were significant differences before and after treatment in the courses in the two groups (P<0.01).</p><p><b>CONCLUSION</b>Both the JIN's 3-needling therapy and the behavior intervention therapy have better therapeutic effects on severe child autism, but the therapeutic effect of JIN's 3-needling is much better.</p>