The use of nanotechnology in medicine holds great promise for revolutionizing a variety of therapies. The past decade witnessed dramatic advancements in scientific research in nanomedicines, although significant challenges still exist in nanomedicine design, characterization, development, and manufacturing. In March 2013, a two-day symposium "Nanomedicines: Charting a Roadmap to Commercialization," sponsored and organized by the Nanomedicines Alliance, was held to facilitate better understanding of the current science and investigative approaches and to identify and discuss challenges and knowledge gaps in nanomedicine development programs. The symposium provided a forum for constructive dialogue among key stakeholders in five distinct areas: nanomedicine design, preclinical pharmacology, toxicology, CMC (chemistry, manufacturing, and control), and clinical development. In this meeting synopsis, we highlight key points from plenary presentations and focus on discussions and recommendations from breakout sessions of the symposium.
The two components, delta pH and delta psi, of the membrane protonmotive force (delta p) effect and are affected by the transport of many substrates and metabolites. Because the integrity (or restoration) of the delta p requires the expenditure of metabolic energy, such transport processes affect the overall cell bioenergetics. However, the transport or high concentrations of certain substrates and metabolites can have more serious effects on cell metabolism because they partially or completely abolish either or both the delta pH and delta psi. If the cells cannot eventually restore the collapsed component(s) of the delta p, complete growth inhibition and cell death become inevitable. In the butanol/acetone fermentation of Clostridium acetobutylicum, the transport and the presence of key metabolites (acetic and butyric acids, and butanol) have serious and some necessary effects on the delta p. Acetic and butyric acids act as uncouplers of the delta pH, thereby reducing the internal pH. Using other acid uncouplers (such as acetoacetate, which is metabolized by the cells, or FCCP, which is not metabolized by the cells), we found that a lower pHo combined with the metabolic-energy drain of the uncoupling effect and high internal acid concentrations are implicated in the mechanism(s) of solventogenesis. Thus, the production or presence (or both) of the two acids (acetic and butyric) is beneficial to the initiation of solvent production. The transport mechanisms of CH3OH, CH2O, and HCOOH in obligate CH3OH utilizers (methylotrophs) were also discussed in detail. We showed that CH3OH is actively transported by the cells at the expense of metabolic energy and that its transport significantly affects the dynamics of continuous bioreactors. The accumulation of CH2O was found to be driven by the membrane delta p. Finally, formate was accumulated by the delta pH according to the general transport mechanism of short-chain fatty acids. The inhibition of growth by formate was explained by its uncoupling effect on the cells. Growth inhibition by CH3OH appeared to be related to the severe reduction of the membrane delta pH and cell pHi by relatively low CH3OH concentrations.
Human coronaviruses (HCoVs) cause respiratory diseases infecting the upper and/or lower respiratory tract. The six human coronaviruses so far identified are HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU-1, SARS-CoV, and MERS-CoV. Four of these coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU-1) are known as circulating common coronavirus found continuously in the human population causing mostly common cold, with few cases of severe diseases. In late December 2019, a novel human coronavirus, now called SARS-CoV-2, was identified during an outbreak in Wuhan, China. The disease spectrum caused by this virus is now called COVID-19 (Coronavirus Infectious disease 2019). This novel coronavirus has spread globally resulting in a world-wide pandemic that continues to rage as of now. SARS-CoV-2 has a high case morbidity and mortality rate and is high risk to the elderly populations, immune-compromised populations, and to those who have other critical issues like heart disease, diabetes, etc.In this review, we summarize the latest information of the epidemiology, pathogenesis, and clinical aspects of SARS-CoV-2, and discuss the current scientific and therapeutic advancements for clinical treatment of this pandemic novel coronavirus. A: Human Coronavirus and its Different Types:Coronaviruses (CoVs) are single-stranded positive-sense RNA viruses whose genome (>27kb) is encapsulated within a lipid membrane envelope carrying spike protein [15]. This envelope is studded with glycoprotein spikes that give coronaviruses their crown-
Airborne and potentially deadly SARS-CoV-2, that causes the disease COVID-19, was discovered in late December of 2019. Till now no medications including vaccine, antibody, or any antiviral are found with success. SARS-CoV-2 is very similar to SARS-CoV-1 which was discovered in 2003, and recognizes the same host cell receptor for entry into the cell. MERS-CoV, another lethal HCoV discovered in 2012, belongs to the same group of SARS (β-type), but recognizes a different cell receptor for host cell entry.All these viruses can only be studied safely under high-level biosafety conditions to protect the laboratory workers and the environment. However, these safety precautions slow down efforts to find drugs and vaccines for COVID-19 since many scientists lack access to the required biosafety facilities.There are four more common human CoVs, such as, HCoV-229E, HCoV-OC43, HCoV-HKU1, and HCoV-NL63, which were known from many years back. They cause self-limiting respiratory infections, such as common cold, in humans, and can be studied safely in BSL2 lab.In this review, a comparison of SARS and Common cold virus were done in order to search for a better surrogate virus those can be used in BSL2 lab for identifying the disease mechanism and therapeutic intervention of SAR-CoV-2. We focused on the following key questions, like, virus-host cell interaction mechanism; the differential cell line susceptibility; species tropism; viral replication efficiency; antigen expression patterns; mechanistic pathway of apoptosis; and structure-function relationship of the virus.
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