A team of biochemists and virologists discovered how human cells would change after being hijacked and infected with SARS-CoV-2. They also found certain compounds that could slow down or stop the virus' reproduction in host cells.
The changes in human cells infected with SARS-CoV-2, the virus of COVID-19, were unveiled by experts at Goethe University and the Frankfurt University Hospital, a leading medical institute in Germany. Their research suggested that the virus minimally influences the protein production of a host cell, compared to other viruses that normally shut down the operation. The minimal influence of the virus might be its weak spot, which could be a target for novel therapies. They published their findings in the journal Nature.
Potential Targets for COVID-19 Therapies Discovered
With so many unknowns about SARS-CoV-2, the international scientific community struggles to develop a vaccine or effective treatments to counter COVID-19. Recent advances in treatment mostly involve the use of existing medications to reduce the severity of symptoms and improve the recovery rate of patients. But none of those are considered as specific treatments for the novel disease. This is why scientists worldwide are busy finding the most optimal solution for all countries.
From Goethe University and the Frankfurt University Hospital, biochemists and virologists joined forces to examine what exactly the virus does in human cells. Their research was more focused on the alterations the virus can do after successfully binding and hijacking host cells. Their efforts yielded substantial insights into the viral mechanisms and cellular parts, which could open potential targets for novel therapies being drafted. One of the insights was the ability of the virus to slightly influence the cellular protein production, a contrast to most other viruses that typically shut the process down.
"Thanks to the mePROD-technology we developed, we were for the first time able to trace the cellular changes upon infection over time and with high detail in our laboratory. We were obviously aware of the potential scope of our findings. However, they are based on a cell culture system and require further testing. The fact that our findings may now immediately trigger further in vivo studies with the purpose of drug development is definitely a great stroke of luck," said Dr. Christian Münch, lead author of the study and Head of the Protein Quality Control Group at the Institute for Biochemistry II at Goethe.
Since February 2020, the Medical Virology at Frankfurt University Hospital has owned an infection cell culture system for SARS-CoV-2. The virus samples they acquired were from the cultivation of the pathogen in colon cells, which were obtained from swab samples from two infected people returning from Wuhan, China. The technique in cultivating and analyzing the virus was developed at Goethe University, leading to the joint research effort.
In the study, the team utilized a specific variant of mass spectrometry called the mePROD method. This was developed a few months earlier. Through that method, the team successfully examined the amount and synthesis rate of thousands of proteins inside a cell. Because of its ability to access those proteins, the team was able to observe how the viral mechanisms of SARS-CoV-2 worked from within. The same mechanisms were observed to detect how much alteration it would do in cellular protein factories. What surprised them was the minimalistic approach of the novel coronavirus.
Normally, viruses attach and penetrate host cells to capture protein factories. The pathogens need to do that to replicate more of its copies by commanding those factories to generate viral proteins. This pattern can be observed in several deadly viral infections. Because most viruses favor replication, they have to suspend the standard protocols of infected cells, which is to produce cellular proteins. The suspension favors higher viral particles to increase the magnitude of infecting other healthy cells. As such, the viral strategy usually signals the immune system of a system-wide invasion.
Meanwhile, SARS-CoV-2 does not suspend the usual protein production of infected cells. The virus influences the process minimally to retain it. While there is no clear explanation yet, the team considers the angle to have potential in novel therapies. Whether or not the virus does that intentionally, the slight impact on the normal protein production in cells may explain why the incubation period of COVID-19 is longer than influenza.
The slight alteration by SARS-CoV-2 is detected 24 hours after infection. The pathogen triggers unique changes to the proteome of the host cell. The cholesterol metabolism is reduced but the carbohydrate metabolism and modification of RNA as protein precursors are aised. The two latter processes are viable targets for therapies.
The team applied compounds in the lab that were designed to inhibit those processes. The compounds successfully hindered the processes. They also tested a substance called 2-deoxy-d-glucose (2-DG) capable of limiting the production of the building blocks for a viral genome, and it was determined successful as well. The preprint edition of the study findings has already caused excitement among scientists in other territories.
COVID-19 Global Deaths Nearing 300,000
According to the World Health Organization, a specialized agency of the United Nations, the total confirmed cases of COVID-19 were 4,248,389 as of May 14, 2020. That total included the 77,965 new cases reported in the past 24 hours. Meanwhile, the total confirmed deaths due to the illness were 294,046, including the 6,647 new deaths in the last 24 hours.
By region, the confirmed total deaths were 1,567 in Africa, 109,121 in the Americas, 9,389 in the Eastern Mediterranean, 163,413 in Europe, 3,921 in Southeast Asia, and 6,622 in the Western Pacific. In the past 24 hours, 67 new deaths were confirmed in Africa, 2,617 in the Americas, 130 in the Eastern Mediterranean, 3,614 in Europe, 175 in Southeast Asia, and 44 in the Western Pacific.
The agency also reported that SARS-CoV-2 is likely prone to disinfectants because of its enveloped structure, compared to non-enveloped viruses, such as norovirus, rotavirus, and poliovirus. Despite the lack of evidence to support airborne transmission, the agency does not ignore its possibility in scenarios wherein aerosolization occurs.
The study findings are essential in the investigation of drugs that can slow down COVID-19. If the substances mentioned in the study are present in certain medications, clinical trials involving those drugs will have a more established basis. And if these drugs can improve COVID-19 symptoms, they may be deployed in clinical settings for patients with moderate or severe symptoms.