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Coronavirus disease-2019 (COVID-19) is a new highly infectious disease caused by a novel coronavirus. Recently, the number of new cases infected pneumonia in the world continues to increase, which has aroused great concern from the international community. At present, there are no small-molecule specific anti-viral drugs for the treatment. The high mortality rate seriously threatens human health. Traditional Chinese medicine (TCM) is a unique health resource in China. The combination of TCM and Western medicine has played a positive and important role in combating COVID-19 in China. In this review, through literature mining and analysis, it was found that TCM has the potential to prevent and treat the COVID-19. Then, the network pharmacological studies demonstrated that TCM played roles of anti-virus, anti-inflammation and immunoregulation in the management of COVID-19 via multiple components acting on multiple targets and multiple pathways. Finally, clinical researches also confirmed the beneficial effects of TCM on the treatment of patients. This review may provide meaningful and useful information on further drug development of COVID-19 and other viral infectious diseases., (Copyright © 2020 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

A strain named NJ2 was isolated from the soils in Nanjing area, and its resting cells transformed IMI into a polar product. The strain was identified as Stenotrophomonas maltophilia based on BioMerieux Vitek system and the analysis of 16S rDNA sequence. Mass spectrometry of the product extracted with an organic solvent and re-crystallization gave m/z value of 272 for the molecular ion while 256 for substrate IMI. It demonstrated that the transformed product was the hydroxylated derivate of IMI or hydroxy IMI. NMR analysis further indicated that the hydroxyl moiety located at the ring of imidazolidine and the transformed product was 5-hydroxy IMI. Kinetics of transformation IMI showed that the content of IMI decreased 1.15 mmol/L and the content of transformed product 5-hydroxy IMI increased 1.10 mmol/L after transformation for 10 days. The molar conversion yield was 95.9%. The S. maltophilia NJ2 strain, with the characterization of strong transformation ability and high molar conversion yield, can be used in industrial production of 5-hydroxy IMI for synthesis of highly insecticidal olefin IMI.

The current technology for microbial hydroxylation of nicotinic acid is a procedure of resting cells transformation. Here it was reported that non-degradation of 6-hydroxynicotinic acid during hydroxylation of nicotinic acid by resting cells was due to existing of nicotinic acid in the transformation mixture, not the death of cells. Therefore it was attempted that the induced cultivation of Pseudomonas putida NA-1 for hydroxylation activity by nicotinic acid was used for accumulation of 6-hydroxynicotinic acid to establish a new technology, a combined technology of growing culture transformation and resting cells transformation. In the combination technology, when 1% of nicotinic acid was kept in cultivation medium by supplement of nicotinic acid at intervals during cultivation of Pseudomonas putida NA-1, the growing culture could consistently hydroxylate nicotinic acid without degradation of its product which was accumulated linearly in the cultivation medium with progress of cultivation; the resting cells obtained from cultivation broth after growing culture transformation still processed a very high hydroxylation activity and could be used to next resting transformation of nicotinic acid. By using of the combined technology, the inducer was saved and the production yield of 6-hydroxynicotinic acid increased above 65%.

Some features of Pseudomonas putida NA-1 strain in cultivation and enzyme production were different from S. marcescens IFO 12648 and P. fluorescens TN5 stains which could transform nicotinic acid to 6-hydroxynicotinic acid reported by other scientists, such as optimal carbon and its optimal concentration, optimal inducer concentration, and optimal cultivation temperature. The ideal transformation condition was nicotinic acid 3%, temperature 35 degrees C and pH 7.0. Under an appropriate condition, in a 4 liter fermenter, production yield of 6-hydroxynicotinic acid by Pseudomonas putida NA-1 was 108.39 g/L.

Strain screening was conducted on a large scale in order to develop a biotransforming process for 6-hydroxynicotinic acid production. A strain named as NA-1 was isolated from soil which could transform nicotinic acid into a new product showed by HPLC. The new product was identified as 6-hydroxynicotinic acid by MS and 1H-NMR. The morphology, physiological and biochemical characteristics of strain NA-1 were studied and showed that characteristics of strain NA-1 were essentially consistent with Pseudomonas putida. The analysis of 16S rDNA sequence from strain NA-1 suggested that strain NA-1 was clustered together with P. putida in phylogenetic tree and the sequence identity between stain NA-1 and Pseudomonas putida was 99%. So strain NA-1 was identified to P. putida.