Can Smart Tools Outsmart The Smartest Virus On The Planet?
Over the past months, the smartest virus on the planet once again made it to the headlines — people of all ages have died from the flu, even the healthy ones that you don’t expect to succumb from this virus. In fact, according to US CDC’s Acting Director, Anne Schuchat, deaths from the current outbreak will probably outnumber those of the 2009-2010 season. The worst flu season in a decade is still not over, with 13 new children deaths recorded bringing the new total to 97 over 3 months of unusually persistent flu infections across the US. As in the past years, most of the children who died this year have not been vaccinated.
The US CDC does not keep exact counts of adult flu deaths but flu-associated deaths in the US range from a low of about 3,000 to a high of about 49,000 people. Yet after the flu season ends, people will once again forget about the hundreds of people who died and how bad the flu season was… until the next flu season comes.
No matter how many times people are reminded to get the vaccine and how often doctors give their patients compelling reasons to get vaccinated, flu shots are always a hard sell because most people are reluctant to think about their chances of getting sick, especially when they are “healthy” and do not get sick anyway. Several myths and fake news articles contribute to why parents resist getting the flu vaccine for themselves and their children. The flu shot is not perfect, preliminary figures released last week suggest that the flu vaccine this year is 36% effective in preventing flu illness. It could have been better, but 36% vaccine effectiveness (VE) is much better than ZERO plus it helps prevent the virus from spreading to the rest of the people in the community.
Since the vaccine protects against several flu strains it is important to note that the effectiveness against flu B was 42% and against H1N1 was 67%. In fact the 25% efficacy against H3N2 is higher than earlier estimates suggesting effectiveness as low as 17% (as seen in Canada).
In addition to vaccines, several novel therapeutic alternatives may prove to be beneficial in the near future. Here are some of the novel approaches that will potentially become effective tools for managing flu infections.
Baloxavir marboxil (S-033188), discovered in Osaka, received preliminary approval in Japan in January 2018 and will be filed for regulatory review in the US and Europe thereafter. The currently available drug, Oseltamivir, works by blocking the neuraminidase that enables a newly-made influenza virus to escape from an infected cell. Baloxavir inhibits cap-dependent endonuclease inhibitor and requires a single dose, unlike Oseltamivir which is taken twice a day for five days.
The long-acting inhaled neuraminidase inhibitor CS-8958 (also known as R-118958) has shown promising results in mouse test subjects for influenza treatment. A polymerase inhibitor, T-705, inhibits viral RNA polymerase — the enzyme responsible for copying a DNA sequence into an RNA sequence during the process of transcription. It has been found to be effective against all three influenza virus types (A, B and C) and to some extent against other RNA viruses, including hemorrhagic fever viruses. The drug, DAS181, is a fusion construct that includes sialidase — an enzyme from Actinomyces Viscosus — a human and animal pathogen that colonizes the mouths of 70% of adult humans. It prevents the virus from attaching to cells.
Chlorogenic acid (CHA) has some antiviral properties, and its inhibitory effect has been demonstrated on Influenza A/PuertoRico/8/1934(H1N1) and Oseltamivir-resistant strains in the late stage of the infectious cycle. Aureonitol, a compound obtained from fungi, has shown inhibitory effects against both influenza A and B virus replication by impairing virus absorption — the first step in the viral life cycle.
AVI-7100, a 20-mer phosphorodiamidate morpholino oligomer (PMO) IV formulation, is a drug that hinders the translation and splicing of mRNA. Splicing is the process by which the precursor messenger RNA (pre-mRNA) transforms into a mature messenger RNA (mRNA). Therefore, protein synthesis is stopped. EV-077 — a dual thromboxane receptor antagonist and thromboxane synthase inhibitor — prevents virus replication by inhibiting prostanoids associated with influenza infections.
Monoclonal antibodies (CR6261 and CR8020) bind to the conserved stalk region (the region that does not mutate often) of HA (hemagglutinin) and inhibit the entry and fusion stages. A broad spectrum human monoclonal antibody (mAb- MEDI8852), which unlike other stem-reactive antibodies, used a rare heavy chain VH (VH6–1) gene, was found to be effective in mice and ferrets and was better than Oseltamivir.
In a new study, researchers reveal that far ultraviolet C (far-UVC) light can kill influenza viruses without negatively affecting human tissues. Researchers suggest that implementing this far-UVC light in places like hospitals, airports, and schools could greatly reduce the incidence of flu infections.
There is no end in sight for the battle between humans and the influenza virus. Unlike smallpox, which has been eradicated from the planet, influenza will be there as long as there are reservoirs (birds, pigs, and other mammals) and as long as influenza undergoes regular mutation. Who will win the battle? Only time will tell.
