Maria Brown

Benefits And Drawbacks Of Covid-19 Biomarker Research And Development

A novel coronavirus strain, “SARS-CoV-2”, has caused havoc around the world. Within two-and-a-half months of its emergence, the WHO declared COVID-19 as a pandemic. Today no antiviral treatment or vaccine is present for COVID-19. Early confirmed detection followed by isolation is the only way to tackle the pandemic. Biomarkers play a crucial role in the current scenario. They help in speeding up the development of novel drugs and the approval of innovative biological products.

SARS-CoV-2 comprises four structural proteins: spike glycoprotein (S), membrane glycoprotein (M), an envelope protein (E), and nucleocapsid protein (N). The viral RNA genome, spike protein, and glycan are the three major biomarker research targets for COVID-19. Let us explore the potential benefits and drawbacks of each of these biomarkers.

Viral RNA genome as a COVID-19 biomarker

Currently, the viral RNA genome is the principal biomarker under study in COVID-19 diagnosis. As the viral genome is a single-stranded RNA, clinical biomarker testing services use RT-PCR as the primary technique in the detection of the viral genome. RT-PCR is sensitive and specific, as it directly detects the viral RNA and amplifies even low levels of viral RNA. However, PCR-based bioanalysis falls short in testing a high volume of samples. Novel assays that use machine learning and high-throughput Sanger sequencing can accommodate high testing demands, but they often require centralized clinical laboratories for efficient bioanalytical detection of the virus.

For a simple, mobile, and rapid detection of the virus, biomarker-testing services need to develop point-of-care testing applications. Several small and rapid detection kits are available for COVID-19. Their detection time ranges from 45 mins to 2-5 mins. However, even when these tests are rapid and readily available, researchers have questioned the accuracy of these point-of-care diagnostic tests. CRISPR-based pk bioanalysis is another alternative to PCR-based tests. The CRISPR molecule detects the viral genetic signature, and upon detection, the CRISPR enzyme activates itself and releases a positive detection signal. CRISPR-based assays are sensitive and can easily be converted into point-of-care tests.

Antibodies binding to the spike protein as biomarkers

Once the virus infects an individual, the adaptive immune system naturally produces antibodies against the S-protein. Upon binding, these antibodies neutralize the S-protein and inhibit the virus from interacting with the human ACE2 receptor. This inhibition hinders the viruses’ ability to infect several cells and thus limits disease progression. Researchers use immunological assays such as ELISA to detect antibodies, proteins, or peptides produced against the S-protein and confirm the presence of the virus. ELISA tests can determine the risk of infection and potential immunity, understand the extent of spread and trace advanced contact infections.

Glycan: emerging biomarker under development for COVID-19

Research has shown that both the host ACE2 receptor and viral S-protein are extensively glycosylated. Glycans are sugar chains present on host cell surfaces. When a virus invades a host via the respiratory tract, they use these glycans. Recent SARS-CoV-2 studies have identified 66 glycosylation sites on the S-protein, out of which each site can occupy up to 10 distinct glycans. Because of its chemical complexity, limited throughput, and sensitivity, we often overlook glycans in COVID-19 research. However, it is crucial to note that, even with its drawbacks, glycans can be helpful as they remain relatively constant compared to the genetic makeup of the virus.

The challenge ahead

Biomarkers have increasingly become an indispensable tool for COVID-19 research. Several novel diagnostics and therapeutics are in the development phase, and the combination and application of biomarker development will be the ultimate antidote against COVID-19.