Key SARS-CoV-2 enzyme behind virus's infectiousness, researchers say

News brief

SARS-CoV-2, the virus that causes COVID-19, is more infectious than severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) viruses because it contains an enzyme that can efficiently circumvent a host cell's innate defense mechanism, Kobe University–led researchers in Japan suggest in the Journal of Virology.

The innate immune system attaches the molecular tag ISG15 to SARS-CoV-2's nucleocapsid protein, which contains the virus's genetic material, inhibiting viral replication. The team's laboratory experiments suggest that the virus's papain-like protease (PLpro) can remove the tag, recovering its ability to assemble new viruses and escape the innate immune response.

Discovery may lead to more effective drugs

While the SARS and MERS viruses belong to the same virus family and also have an enzyme that can remove the ISG15 tag, their versions are less efficient and have a different primary target than that of SARS-CoV-2.

We may be able to develop new antiviral drugs if we can inhibit the function of the viral enzyme that removes the ISG15 tag.

Ikuo Shoji, MD, PhD

In a Kobe University news release today, senior author Ikuo Shoji, MD, PhD, said this finding may help guide the development of more effective and selective COVID-19 inhibitors that target SARS-CoV-2's nucleocapsid protein.

"We may be able to develop new antiviral drugs if we can inhibit the function of the viral enzyme that removes the ISG15 tag," he said. "Future therapeutic strategies may also include antiviral agents that directly target the nucleocapsid protein, or a combination of these two approaches."

Germany reports first mpox case from new clade

News brief

Stephanie Soucheray, MA

The Robert Koch Institute in Germany says the country has its first case of mpox cause by a new, more virulent variant causing a massive outbreak in Africa.

The case-patient recently traveled abroad, but few other details were given by the institute.

Germany is now the third country outside of Africa to report infections with what is being called mpox clade 1b. In August, Sweden and Thailand both reported a case.

DR Congo hardest hit

The Democratic Republic of the Congo has recorded the most cases of clade 1b, with the outbreak spreading to 17 neighboring countries on the continent and 1,100 deaths now confirmed in Africa.

According to the Africa Centres for Disease Control and Prevention, there have been 42,438 reported cases, with 8,113 confirmed as mpox, in Africa in 2024.

Study: XEC characteristics position COVID variant to become dominant

News brief

Lisa Schnirring

The XEC variant will likely become the world’s predominant SARS-CoV-2 variant in the near future, researchers from the Sato Lab, based at the University of Tokyo, reported recently in a preprint study.

XEC—first identified in Germany in early August—is a recombinant of two JN.1 descendant lineages, KS.1.1 and KP.3.3. In the United States, the KP.3.1.1 variant is still dominant and rising, making up an estimated 57.2% of SARS-CoV-2 viruses, the Centers for Disease Control and Prevention (CDC) said in its latest projections. However, it also noted a steady rise in XEC viruses, which make up about 10.7% of sequenced samples.

In comments on the study on X, Kei Sato, PhD, who leads the lab, said researchers compared the XEC variant with KP.3.1.1, finding that XEC has two spike mutations, compared to KP.3. The group’s phylogenetic epidemic dynamics modeling, based on surveillance from five countries, suggests that the reproduction number of XEC is greater than that of KP.3.1.1, which is currently the world’s dominant virus. The reproduction number is the average number of additional cases generated by each case in a susceptible population.

Increased infectivity, more immune-evasive

When the researchers examined virological properties with pseudovirus experiments, they found that the increase in infectivity was due to one of the two spike mutations (S:F59S) in XEC.

Experiments with XBB.1.5 and JN.1 sera to assess breakthrough infection found that neutralization titers for XEC and KP.3.1.1 were similar. However, compared to KP3.3 sera, neutralization against XEC was significantly lower than that of KP.3.1.1, and both mutations significantly increased resistance to KP.3.3 sera, suggestive of higher immune evasion.

Sato wrote that the higher reproduction number of XEC when compared to KP3.1.1 is partly attributed to the more robust resistance to KP.3.3.