Konstantin Andreev

• Ph.D. in Biology
• Postdoctoral Research Fellow at St. Jude Children's Research Hospital

Testing approved antivirals against A(H5N1) influenza viruses circulating in peridomestic species, including dairy cows, is critical to public health and pre-pandemic planning. It cannot be tested in humans due to A(H5N1) disease severity. Here, in mice, we demonstrate that US FDA-approved baloxavir treatment mediates improved disease outcomes (sur...

In March 2024, clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses were first detected in U.S. dairy cattle. Similar viruses have since caused 66 zoonotic human infections. To assess changes to zoonotic potential, we characterized A(H5N1) clade 2.3.4.4b viruses isolated from cows’ milk and birds. Bovine-derived viruses were lethal in m...

Understanding the reliability of FDA-approved antivirals against A(H5N1) influenza viruses circulating in peridomestic species including dairy cows is critical to public health and pre-pandemic planning, but it cannot be modeled clinically due to A(H5N1) disease severity. In mice, we demonstrate baloxavir treatment mediates greater disease outcomes...

Highly pathogenic avian influenza (HPAI) viruses have spread at an unprecedented scale, leading to mass mortalities in birds and mammals. In 2023, a transatlantic incursion of HPAI A(H5N5) viruses into North America was detected, followed shortly thereafter by a mammalian detection. As these A(H5N5) viruses were similar to contemporary viruses desc...

The antiviral susceptibility of currently circulating (2022–2023) highly pathogenic avian influenza (HPAI) A(H5N1) viruses was assessed by genotypic and phenotypic approaches. The frequency was low for neuraminidase (NA) and polymerase acidic (PA) substitutions associated with reduced inhibition by NA inhibitors (21/2698, 0.78%) or the PA inhibitor...

Aberrant levels of glycolipids expressed on cellular surfaces are characteristic of different types of cancers. The oligomer of acylated lysine (OAK) mimicking antimicrobial peptides displays in vitro activity against human and murine melanoma cell lines with upregulated GD3 and GM3 gangliosides. Herein, we demonstrate the capability of OAK to inte...

The cover art depicts the arrangement of surfactant components at the alveolar surface in lungs. Vesicles of pulmonary surfactant in the subphase prevent interfacial monolayers from collapse by expanding the ordered phase. The phospholipid‒cholesterol distribution displays a hexagonal unit cell revealed by X-ray diffraction. Cover design conceived...

When compressed by the shrinking alveolar surface area during exhalation, films of pulmonary surfactant in situ reduce surface tension to levels at which surfactant monolayers collapse from the surface in vitro. Vesicles of pulmonary surfactant added below these monolayers slow collapse. X-ray scattering here determined the structural changes induc...

When compressed by the shrinking alveolar surface area during exhalation, films of pulmonary surfactant in situ reduce surface tension to levels, at which surfactant monolayers collapse from the surface in vitro . Vesicles of pulmonary surfactant added below these monolayers slow collapse. X-ray scattering here determined the structural changes tha...

Pulmonary surfactant is the mixture of lipids and proteins that lowers surface tension in the lungs. The material forms a thin film on the aqueous layer that lines the alveolar air-sacks. When compressed by the shrinking alveolar surface area during exhalation, the surfactant film achieves surface tensions < 5 mN/m. The molecular arrangement of the...

Background Gangliosides are an essential component of eukaryotic plasma membranes implicated in multiple physiological processes. Little is known about molecular mechanisms underlying the distribution and functions of membrane gangliosides. The overwhelmingly complex organization of glycocalyx impedes the structural analysis on cell surface and the...

Gram-negative bacteria are protected from their environment by an outer membrane that is primarily composed of lipopolysaccharides (LPS). Under stress, pathogenic serotypes of Salmonella enterica remodel their LPS through the PhoPQ two-component regulatory system that increases resistance to both conventional antibiotics and antimicrobial peptides...

Synthetic polymers mimicking antimicrobial peptides have drawn considerable interest as potential therapeutics. N‐substituted glycines, or peptoids, are recognized by their in vivo stability and ease of synthesis. Peptoids are thought to act primarily on the negatively charged lipids that are abundant in bacterial cell membranes. A mechanistic unde...

Cancer is one of the most serious threats to global public health. Aside from the surgical treatment, radiation and immunotherapy, chemotherapeutic approaches remain at the frontline of curative and palliative care for oncology diseases. Due to the current limitations of conventional chemotherapies, identifying potential targets for novel anticance...

The outermost surface of Gram-negative bacteria is almost entirely composed of lipopolysaccharides. These lipids are targeted by host defense peptides as an innate immune response. Pathogenic serotypes of Salmonella enterica possess the two-component regulatory system, PhoPQ, that modifies lipopolysaccharides in response to the presence of host def...

Hydrophobic interactions govern specificity for natural antimicrobial peptides. No such relationship has been established for synthetic peptoids that mimic antimicrobial peptides. Peptoid macrocycles synthesized with five different aromatic groups are investigated by minimum inhibitory and hemolytic concentration assays, epifluorescence microscopy,...

Nature is a major source of inspiration for drug design. Bacteria are developing resistance towards conventional antibiotics. Utilizing antimicrobial peptides (AMPs) – an essential component of innate immune system, as therapeutic agents, may be a viable alternative. Unfortunately, there are a number of serious hurdles on the way towards clinical a...

The peptidomimetic approach has emerged as a powerful tool for overcoming the inherent limitations of natural antimicrobial peptides, where the therapeutic potential can be improved by increasing selectivity and bioavailability. Restraining conformational flexibility of a molecule may reduce the entropy loss upon its binding to the membrane. Experi...

Small hydrophilic antibiotics traverse the outer membrane of Gram-negative bacteria through porin channels. Large lipophilic agents traverse the outer membrane through its bilayer, containing a majority of lipopolysaccharides in its outer leaflet. Genes controlled by the two-component regulatory system PhoPQ modify lipopolysaccharides. We isolate l...

A promising class of potential new antibiotics are the antimicrobial peptides or their synthetic mimics. Herein we assess the effect of the type of cationic side chain (i.e., guanidino vs. amino groups) on the membrane perturbing mechanism of antimicrobial α-peptide-β-peptoid chimeras. Two separate Langmuir monolayers composed of 1,2-dipalmitoyl-sn...

In this investigation, three complimentary experimental techniques including atomic force microscopy (AFM), X-ray reflectivity (XR), and epiflourescence microscopy (EFM) were employed to determine the mechanism of action of the antimicrobial cyclic peptoid ML2-6 on model mammalian and bacteria membrane systems. Mammalian and bacterial membranes wer...

Pulmonary surfactant (PS) is the complex mixture of lipids and proteins that forms a thin film on the liquid layer that lines the alveolar air-sacks of the lungs. When compressed by the decreasing alveolar surface area during exhalation, the surfactant films reduce surface tension to exceptionally low levels. This behavior in situ contrasts with th...

Non-natural oligomeric mimics of antimicrobial peptides (AMPs) can be designed to display chemical moieties analogous to the active side chains of natural peptides, while their abiotic backbone provides protection from proteolytic degradation. N-substituted glycine oligomers (peptoids) are an outstanding example of potential anti-infectious agents...

Synthetic compounds mimicking the structure of natural antimicrobial peptides (AMPs) have a great promise as potential anti-infectious agents due to their stability towards enzymatic degradation, high antibiotic efficiency, and broad adjustability of physicochemical properties. Recently we have demonstrated that antimicrobial activity of AMP synthe...