Small molecules in the treatment of COVID-19

The outbreak of COVID-19 has become a global crisis,and brought severe disruptions to societies and economies.Until now,effective therapeutics against COVID-19 are in high demand.Along with our improved understanding of the structure,function,and pathogenic process of SARS-CoV-2,many small molecules with potential anti-COVID-19 effects have been developed.So far,several antiviral strategies were explored.Besides directly inhibition of viral proteins such as RdRp and M^(pro),interference of host enzymes including ACE2 and proteases,and blocking relevant immunoregulatory pathways represented by JAK/STAT,BTK,NF-κB,and NLRP3 pathways,are regarded feasible in drug development.The development of small molecules to treat COVID-19 has been achieved by several strategies,including computer-aided lead compound design and screening,natural product discovery,drug repurposing,and combination therapy.Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries.And many candidates have entered clinical-trial stage.Nevertheless,due to the epidemiological features and variability issues of SARS-CoV-2,it is necessary to continue exploring novel strategies against COVID-19.This review discusses the current findings in the development of small molecules for COVID-19 treatment.Moreover,their detailed mechanism of action,chemical structures,and preclinical and clinical efficacies are discussed.

Design and Performance Study of an Ultrasonic Bone Scalpel with Composite Horn Structure

The ultrasonic bone scalpel was often used in all kinds of clinical orthopedic surgery as a new type of medical instrument.Based on the working theory of the ultrasonic bone scalpel and combined with the design method of a quarter wavelength transducer and horn,this study proposed an optimization design method for the ultrasonic bone scalpel with a composite horn structure.The structure of the ultrasonic bone scalpel was simplified,and its length was shortened.Finite element analysis,modal analysis,and harmonic response analysis were used to optimize the design of the ultrasonic bone scalpel.The performance of the ultrasonic bone scalpel was explored through impedance analysis,amplitude measurement,temperature measurement,and cutting tests,and the feasibility of the design was verified through torque analysis.The results showed that when the torque force was 4.0 N,the resonance frequency of the ultrasonic bone scalpel was 30,540 Hz,and the maximum amplitude of the ultrasonic bone scalpel could reach 62μm.After spray cooling,the maximum surface temperature of the rear end cover was reduced from 51.8 to 36.3℃,the maximum surface temperature of the composite horn was reduced from 71 to 45.3℃,and the maximum surface temperature of the cutter head was reduced from 101 to 46.1℃,demonstrating a good cooling effect.Under 89 Voltage,the optimal cutting force for cutting chicken leg bones was 0.1 N,the optimal cutting force for cutting pork ribs was 0.3 N,and the cutting process showed tissue selectivity.