Markus Hoffmann

Markus Hoffmann
German Primate Center | DPZ · Infection Biology Unit

Dr. rer. nat.

About

140
Publications
36,650
Reads
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20,265
Citations
Additional affiliations
January 2015 - April 2020
German Primate Center
Position
  • PostDoc Position
Description
  • 1.) Entry process of emerging viruses 2.) Activation of viral glycoproteins 3.) Identification of targets for antiviral therapy
June 2014 - December 2014
German Primate Center
Position
  • PostDoc Position
Description
  • 1.) Prions: Establishment/Refinement of BSE detection methods; Risk assessment studies for chronic wasting disease (CWD) 2.) Virus-host-interaction: Changes in cell. miRNA profiles after infection; Virus-encoded miRNAs
October 2009 - May 2014
University of Veterinary Medicine Hannover
Position
  • PhD Student
Description
  • - Functional characterization of spike glycoproteins of SARS-CoV-related bat viruses: Species tropism, cell entry, receptors, proteolytic activation - Virus-cell-interactions of (potentially) zoonotic viruses linked to bats/flying foxes
Education
October 2002 - December 2007
Leibniz Universität Hannover
Field of study
  • Biology

Publications

Publications (140)
Article
Full-text available
The transmembrane serine protease 2 (TMPRSS2) primes the SARS-CoV-2 Spike (S) protein for host cell entry and represents a promising target for COVID-19 therapy. Here we describe the in silico development and in vitro characterization of peptidomimetic TMPRSS2 inhibitors. Molecular docking studies identified peptidomimetic binders of the TMPRSS2 ca...
Article
Full-text available
In light of the decreasing immune protection against symptomatic SARS-CoV-2 infection after initial vaccinations and the now dominant immune-evasive Omicron variants, ‘booster’ vaccinations are regularly performed to restore immune responses. Many individuals have received a primary heterologous prime-boost vaccination with long intervals between v...
Article
Full-text available
The interferon-induced host cell protein shiftless (SFL) was reported to inhibit human immunodeficiency virus (HIV) infection by blocking the –1 programmed ribosomal frameshifting (–1PRF) required for expression of the Gag-Pol polyprotein. However, it is not clear how SFL inhibits –1PRF. To address this question, we focused on a 36 amino acids comp...
Article
The redox status of the cysteine-rich SARS-CoV-2 spike glycoprotein (SARS-2-S) is important for binding of SARS-2-S to ACE2, suggesting that drugs with a functional thiol group ("thiol drugs") may cleave cystines to disrupt SARS-CoV-2 cell entry. In addition, neutrophil-induced oxidative stress is a mechanism of COVID-19 lung injury, and the antiox...
Article
Full-text available
Effective vaccines and monoclonal antibodies have been developed against coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). However, the appearance of virus variants with higher transmissibility and pathogenicity is a major concern because of their potential to escape vaccines and clinically...
Article
Full-text available
TRIANNI mice carry an entire set of human immunoglobulin V region gene segments and are a powerful tool to rapidly isolate human monoclonal antibodies. After immunizing these mice with DNA encoding the spike protein of SARS-CoV-2 and boosting with spike protein, we identified 29 hybridoma antibodies that reacted with the SARS-CoV-2 spike protein. N...
Article
Full-text available
Neutralizing antibodies against SARS‐CoV‐2 are important to protect against infection and/or disease. Using an assay to detect antibodies directed against the receptor binding domain (RBD) of SARS‐CoV‐2 Spike, we identified individuals with SARS‐CoV‐2 infection after an outbreak at a local health institution. All but one COVID‐19 patient developed...
Article
The Omicron variant of SARS-CoV-2 evades antibody-mediated neutralization with unprecedented efficiency. At least three Omicron sublineages have been identified, BA.1, BA.2 and BA.3, with BA.2 exhibiting increased transmissibility. However, it is currently unknown whether BA.2 differs from the other sublineages regarding cell entry and antibody-med...
Article
Full-text available
SARS-CoV-2 variants of concern (VOC) acquired mutations in the spike (S) protein, including E484K, that confer resistance to neutralizing antibodies. However, it is incompletely understood how these mutations impact viral entry into host cells. Here, we analyzed how mutations at position 484 that have been detected in COVID-19 patients impact cell...
Article
Full-text available
Mutations in the spike protein generated a highly infectious and transmissible D614G variant, which is present in newly evolved fast-spreading variants. The D614G, Alpha, Beta, and Delta spike variants of SARS-CoV-2 appear to expedite membrane fusion process for entry, but the mechanism of spike-mediated fusion is unknown. Here, we reconstituted an...
Article
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Rapid spread of SARS-CoV-2 variants C.1.2 and B.1.621 (Mu variant) in Africa and the Americas, respectively, as well as a high number of mutations in the viral spike proteins raised concerns that these variants might pose an elevated threat to human health. Here, we show that C.1.2 and B.1.621 spike proteins mediate increased entry into certain cel...
Article
Full-text available
Several SARS-CoV-2 variants emerged that harbor mutations in the surface unit of the viral spike (S) protein that enhance infectivity and transmissibility. Here, we analyzed whether ten naturally-occurring mutations found within the extended loop harboring the S1/S2 cleavage site of the S protein, a determinant of SARS-CoV-2 cell tropism and pathog...
Preprint
Introduction The ongoing COVID-19 pandemic situation caused by SARS-CoV-2 and variants of concern such as B.1.617.2 (Delta) and recently, B.1.1.529 (Omicron) is posing multiple challenges to humanity. The rapid evolution of the virus requires adaptation of diagnostic and therapeutic applications. Objectives In this study, we describe camelid heavy...
Article
Background: Coronavirus disease 2019 (COVID-19) as global pandemic disease has been adversely affecting public health and social life with considerable loss of human life worldwide. Therefore, there is an urgent need for developing novel therapeutics to combat COVID-19. The causative agent of COVID-19 is SARS-CoV-2 which targets human angiotensin...
Article
Recent emergence of SARS CoV-2 variants demonstrates the potential of this virus for targeted evolution, despite its overall genomic stability. Here we show the dynamics and the mechanisms behind the rapid adaptation of SARS-CoV-2 to growth in Vero E6 cells. The selective advantage for growth in Vero E6 cells is due to increased cleavage efficiency...
Article
Full-text available
Coronavirus disease 2019 (COVID-19), the illness caused by a novel coronavirus now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 260 million confirmed infections and 5 million deaths to date. While vaccination is a powerful tool to control pandemic spread, medication to relieve COVID-19-associated symptom...
Article
Full-text available
Global pandemics caused by influenza or coronaviruses cause severe disruptions to public health and lead to high morbidity and mortality. There remains a medical need for vaccines against these pathogens. CMV (cytomegalovirus) is a β-herpesvirus that induces uniquely robust immune responses in which remarkably large populations of antigen-specific...
Article
Full-text available
Since the beginning of the COVID-19 pandemic, multiple SARS-CoV-2 variants have emerged. While some variants spread only locally, others, referred to as variants of concern, disseminated globally and became drivers of the pandemic. All SARS-CoV-2 variants harbor mutations relative to the virus circulating early in the pandemic, and mutations in the...
Article
Full-text available
Background Heterologous COVID-19 vaccination regimens combining vector- and mRNA-based vaccines are already administered, but data on solicited adverse reactions, immunological responses and elicited protection are limited. Methods To evaluate the reactogenicity and humoral as well as cellular immune responses towards most prevalent SARS-CoV-2 var...
Preprint
Full-text available
Reports suggest that COVID-19 vaccine effectiveness is decreasing, either due to waning immune protection, emergence of new variants of concern, or both. Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA vaccine (e.g. BNT162b2, BNT) appeared to be superior in inducing protective immunity,...
Preprint
Full-text available
Reports suggest that COVID-19 vaccine effectiveness is decreasing, either due to waning immune protection, emergence of new variants of concern, or both. Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA vaccine (e.g. BNT162b2, BNT) appeared to be superior in inducing protective immunity,...
Preprint
Full-text available
Background: SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection. The novel variant of concern Omicron (B.1.1.529) has to date the largest number of amino acid alterations in its Spike protein. Thus, it may efficiently escape recognition by neutralizing antibodies, allowing breakthrough i...
Preprint
Full-text available
The rapid spread of the SARS-CoV-2 Omicron variant suggests that the virus might become globally dominant. Further, the high number of mutations in the viral spike-protein raised concerns that the virus might evade antibodies induced by infection or vaccination. Here, we report that the Omicron spike was resistant against most therapeutic antibodie...
Article
The rapid spread of the SARS-CoV-2 Omicron variant suggests that the virus might become globally dominant. Further, the high number of mutations in the viral spike-protein raised concerns that the virus might evade antibodies induced by infection or vaccination. Here, we report that the Omicron spike was resistant against most therapeutic antibodie...
Article
Full-text available
Several effective SARS-CoV-2 vaccines are currently in use, but effective boosters are needed to maintain or increase immunity due to waning responses and the emergence of novel variants. Here we report that intranasal vaccinations with adenovirus 5 and 19a vectored vaccines following a systemic plasmid DNA or mRNA priming result in systemic and mu...
Article
Full-text available
The bat sarbecovirus RaTG13 is a close relative of SARS-CoV-2, the cause of the COVID-19 pandemic. However, this bat virus was most likely unable to directly infect humans since its Spike (S) protein does not interact efficiently with the human ACE2 receptor. Here, we show that a single T403R mutation increases binding of RaTG13 S to human ACE2 and...
Article
Full-text available
To monitor infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and successful vaccination against coronavirus disease 2019 (COVID-19), the kinetics of neutralizing or blocking anti-SARS-CoV-2 antibody titers need to be assessed. Here, we report the development of a quick and inexpensive surrogate SARS-CoV-2 blocking assay...
Article
Full-text available
The host cell serine protease TMPRSS2 is an attractive therapeutic target for COVID-19 drug discovery. This protease activates the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of other coronaviruses and is essential for viral spread in the lung. Utilizing rational structure-based drug design (SBDD) coupled to su...
Article
Full-text available
Natural or experimental infection of domestic cats and virus transmission from humans to captive predatory cats suggest that felids are highly susceptible to SARS-CoV-2 infection. However, it is unclear which cells and compartments of the respiratory tract are infected. To address this question, primary cell cultures derived from the nose, trachea,...
Preprint
Full-text available
The interactions between severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and human host factors enable the virus to propagate infections that lead to COVID-19. The spike protein is the largest structural component of the virus and mediates interactions essential for infection, including with the primary ACE2 receptor. We perfor...
Preprint
Full-text available
Defective interfering (DI) RNAs arise during influenza virus replication, can be packaged into particles (DIPs) and suppress spread of wildtype (WT) virus. However, the molecular signatures of DI RNAs and the mechanism underlying antiviral activity are incompletely understood. Here, we show that any central deletion is sufficient to convert a viral...
Article
Full-text available
Currently approved viral vector-based and mRNA-based vaccine approaches against coronavirus disease 2019 (COVID-19) consider only homologous prime-boost vaccination. After reports of thromboembolic events, several European governments recommended using AstraZeneca’s ChAdOx1-nCov-19 (ChAd) only in individuals older than 60 years, leaving millions of...
Article
Full-text available
The Delta variant of SARS-CoV-2, B.1.617.2, emerged in India and has spread to over 80 countries. B.1.617.2 replaced B.1.1.7 as the dominant virus in the United Kingdom, resulting in a steep increase in new infections, and a similar development is expected for other countries. Effective countermeasures require information on susceptibility of B.1.6...
Article
Full-text available
SARS-CoV-2, the cause of the COVID-19 pandemic, exploits host cell proteins for viral entry into human lung cells. One of them, the protease TMPRSS2, is required to activate the viral spike protein (S). Even though two inhibitors, camostat and nafamostat, are known to inhibit TMPRSS2 and block cell entry of SARS-CoV-2, finding further potent therap...
Article
Full-text available
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants,...
Article
The spike protein of SARS-CoV-2 harbours a cleavage motif for host cell proteases that is not found in closely related viruses. Peacock and colleagues show that this motif allows the virus to evade innate antiviral defences and is required for transmission.
Preprint
Full-text available
The delta variant of SARS-CoV-2, B.1.617.2, emerged in India and has subsequently spread to over 80 countries. B.1.617.2 rapidly replaced B.1.1.7 as the dominant virus in the United Kingdom, resulting in a steep increase in new infections, and a similar development is expected for other countries. Effective countermeasures require information on su...
Article
Background Vaccine-induced neutralizing antibodies are key in combating the COVID-19 pandemic. However, delays of boost immunization due to limited availability of vaccines may leave individuals vulnerable to infection and prolonged or severe disease courses. The emergence of SARS-CoV-2 variants of concern (VOC), B.1.1.7 (United Kingdom), B.1.351 (...
Preprint
Full-text available
Cerebral venous thrombosis was reported as a rare but serious adverse event in young and middle-aged vaccinees following immunization with AstraZeneca's ChAdOx1-nCov-19 vaccine. As a consequence, several European governments recommended using this vaccine only in individuals older than 60 years leaving millions of ChAd primed individuals with the d...
Preprint
Full-text available
We investigated immune response in vaccinees vaccinated either with ChAdOx/ChAdOx or ChAdOx/BNT. We testet B and T cell-mediated immune resonses. More profound immune response after heterologous vaccination in both arms. Heterologous immunization very effcient in inducing neutralizing antibodies directed against the current varriants of concern.
Preprint
Background Heterologous prime-boost schedules with vector- and mRNA-based COVID-19 vaccines are already administered, but immunological responses and elicited protection have not been reported. Methods We here analyzed a cohort of 26 individuals aged 25-46 (median 30.5) years that received a ChAdOx1 nCoV-2019 prime followed by a BNT162b2 boost afte...
Preprint
Full-text available
Cerebral venous thrombosis was reported as a rare but serious adverse event in young and middle-aged vaccinees following immunization with AstraZeneca’s ChAdOx1-nCov-19 vaccine. As a consequence, several European governments recommended using this vaccine only in individuals older than 60 years leaving millions of ChAd primed individuals with the d...
Article
Full-text available
The emergence of SARS-CoV-2 variants threatens efforts to contain the COVID-19 pandemic. The number of COVID-19 cases and deaths in India has risen steeply and a SARS-CoV-2 variant, B.1.617, is believed to be responsible for many of these cases. The spike protein of B.1.617 harbors two mutations in the receptor binding domain, which interacts with...
Preprint
Full-text available
Global pandemics by influenza or coronaviruses cause severe disruptions to the public health and lead to severe morbidity and mortality. Vaccines against these pathogens remain a medical need. CMV (cytomegalovirus) is a β-herpesvirus that induces uniquely robust immune responses, where outstandingly large populations of antigen-specific CD8+ T cell...
Preprint
The host cell serine protease TMPRSS2 is an attractive therapeutic target for COVID-19 drug discovery. This protease activates the Spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and of other coronaviruses and is essential for viral spread in the lung. Utilizing rational structure-based drug design (SBDD) coupled to su...
Preprint
The emergence of SARS-CoV-2 variants threatens efforts to contain the COVID-19 pandemic. The number of COVID-19 cases and deaths in India has risen steeply in recent weeks and a novel SARS-CoV-2 variant, B.1.617, is believed to be responsible for many of these cases. The spike protein of B.1.617 harbors two mutations in the receptor binding domain,...
Article
Full-text available
The high transmissibility of SARS-CoV-2 is related to abundant replication in the upper airways, which is not observed for the other highly pathogenic coronaviruses SARS-CoV and MERS-CoV. We here reveal features of the coronavirus spike (S) protein, which optimize the virus towards the human respiratory tract. First, the S proteins exhibit an intri...
Article
Full-text available
The acid sphingomyelinase/ceramide system has been shown to be important for cellular infection with at least some viruses, for instance rhinovirus or SARS-CoV-2. Functional inhibition of the acid sphingomyelinase using tricyclic antidepressants prevented infection of epithelial cells, for instance with SARS-CoV-2. The structure of ambroxol, i.e. t...