Chinese researchers have found a link between lower levels of a small molecule in diabetic patients and the risk of developing severe Covid-19, saying supplements might be able to help reduce the danger.
Diabetic patients have higher risk of becoming seriously ill or dying from Covid-19, but the reasons why are not fully understood.
In a paper published in the peer-reviewed online journal Nature Metabolism on Monday, the researchers found that supplements of 1,5-AG, a blood biomarker for human diabetes, could reduce replication of the coronavirus in mice.
“These results indicate that 1,5-AG is an effective anti-Sars-CoV-2 serum metabolite that is downregulated by diabetes,” the authors wrote.
Cheng Gong, a professor at Tsinghua University’s school of medicine and a lead author of the paper, said the study showed diabetes patients could reduce the risk of developing severe Covid-19 by elevating the level of 1,5-AG, and there were different means to do that.
“The level of 1,5-AG negatively correlated with blood glucose concentration. Clinically, if the level of blood glucose can effectively be reduced, the level of 1,5-AG will be elevated and reduce the risk of developing Covid-19,” Cheng said.
He said the researchers were working on a 1,5-AG supplement in slow-release capsules and the results were promising.
In the meantime, diabetes patients could still benefit from the study by eating food rich in 1,5-AG, such as soybeans. Cheng said 1,5-AG was not toxic and did not have major adverse effects.
Some molecules in blood related to metabolic processes, known as metabolites, vary significantly in quantity and composition among individuals.
The researchers from several Chinese institutions, including Tsinghua University, the Shenzhen Centre for Disease Control and Prevention, and the Academy of Military Medical Sciences, explored whether some of these metabolites might regulate Sars-CoV-2, the virus that causes Covid-19.
They identified several metabolites that are linked with reduced amounts of the RNA of the coronavirus, including 1,5-AG.
In diabetes patients, the level of 1,5-AG in serum was much lower – about five to 10 times – than that in healthy people, but there was no difference in the levels of other two metabolites that researchers found to reduce the virus RNA.
Lab experiments showed that the virus replication was higher in the diabetes’ patients serum but it was reduced by supplementation of 1,5-AG.
Researchers found that 1,5-AG inhibited Sars-CoV-2 infection by directly binding to two sites of the S2 Subunit, one part of the spike protein of the coronavirus that controls infection, and interrupts the process.
They compared sequences of all the variants of concern and found the two sites of the S2 subunit the 1,5-AG acted on were stable in all variants, suggesting the metabolite’s role would be still stable.
It does not influence the infection of some common respiratory viruses, suggesting 1,5-AG had potential in the specific resistance of human coronaviruses, according to the authors.
In experiments on mice, they found that mice treated with 1,5-AG had much lower viral loads and less severe lung damage than the control group.
“These results suggest that 1,5-AG deficiency accounts for severe Sars-CoV-2 pathogenesis in diabetic mice,” the authors wrote.
“Sustained supplementation of 1,5-AG to a healthy level in diabetic mice restored the Sars-CoV-2 loads and disease severity to a lower level in the nondiabetic mice.
“Our results suggest that a low level of 1,5-AG in diabetic people might, in part, underlie a high risk for severe Covid-19 … suggesting that 1,5-AG supplementation and amelioration of hyperglycemia in patients with diabetes might help to reduce the incidence and or prevent severe Covid-19.”
Editor: Guo Lili
